2-arm Trial of Paclitaxel Plus Bevacizumab vs. Capecitabine Plus Bevacizumab (TURANDOT)

• ClinicalTrials.gov Identifier: NCT00600340
• Recruitment Status: Completed
• First Posted: January 25, 2008
• Results First Posted: December 30, 2019
• Last Update Posted: December 30, 2019
• Sponsor: Central European Cooperative Oncology Group
• Information provided by (Responsible Party): Central European Cooperative Oncology Group

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Breast Cancer
• Interventions: Biological: Bevacizumab and Paclitaxel; Biological: Bevacizumab and Capecitabine
• Enrollment: 564

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description	Bevacizumab 10 mg/kg i.v., days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine twice-daily 1000 mg/m², day 1 to 14, every 3 weeks
Period Title: Overall Study
Started	285	279
Completed	285	279
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine	Total
Arm/Group Description		Bevacizumab 10 mg/kg i.v., days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine twice-daily 1000 mg/m², day 1 to 14, every 3 weeks	Total of all reporting groups
Overall Number of Baseline Participants		285	279	564
Baseline Analysis Population Description		Intention-to-Treat Population (ITT)
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	218 76.5%	201 72.0%	419 74.3%
	>=65 years	67 23.5%	78 28.0%	145 25.7%
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	285 participants	279 participants	564 participants
		59; (49 to 64)	59; (48 to 65)	59; (49 to 65)
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	285 participants	279 participants	564 participants
		56.5 (10.98)	56.6 (11.67)	56.6 (11.32)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Female	284 99.6%	275 98.6%	559 99.1%
	Male	1 0.4%	4 1.4%	5 0.9%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Caucasian/ White	283 99.3%	278 99.6%	561 99.5%
	Black	1 0.4%	0 0.0%	1 0.2%
	Other	1 0.4%	1 0.4%	2 0.4%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Austria	Number Analyzed	285 participants	279 participants	564 participants
		38	37	75
Latvia	Number Analyzed	285 participants	279 participants	564 participants
		15	12	27
Romania	Number Analyzed	285 participants	279 participants	564 participants
		20	22	42
Hungary	Number Analyzed	285 participants	279 participants	564 participants
		82	80	162
Czechia	Number Analyzed	285 participants	279 participants	564 participants
		18	19	37
Poland	Number Analyzed	285 participants	279 participants	564 participants
		19	17	36
Slovakia	Number Analyzed	285 participants	279 participants	564 participants
		6	9	15
Israel	Number Analyzed	285 participants	279 participants	564 participants
		54	51	105
Bulgaria	Number Analyzed	285 participants	279 participants	564 participants
		7	6	13
Serbia	Number Analyzed	285 participants	279 participants	564 participants
		6	8	14
Bosnia and Herzegovina	Number Analyzed	285 participants	279 participants	564 participants
		13	13	26
Croatia	Number Analyzed	285 participants	279 participants	564 participants
		7	5	12
Menopausal status; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Pre-menopausal	52 18.2%	52 18.6%	104 18.4%
	Post-menopausal	232 81.4%	223 79.9%	455 80.7%
	Male patients	1 0.4%	4 1.4%	5 0.9%
Eastern Cooperative Oncology Group Performance Status (ECOG PS) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	0	193 67.7%	179 64.2%	372 66.0%
	1	75 26.3%	91 32.6%	166 29.4%
	2	16 5.6%	7 2.5%	23 4.1%
	Missing	1 0.4%	2 0.7%	3 0.5%
		[1] Measure Description: 0 - Asymptomatic, 1 - Symptomatic but completely ambulatory, 2 - Symptomatic, <50% in bed during the day, 3 - Symptomatic, >50% in bed, but not bedbound, 4 - Bedbound, 5 - Death
Estrogen receptor (ER); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Positive	215 75.4%	201 72.0%	416 73.8%
	Negative	68 23.9%	77 27.6%	145 25.7%
	Unknown	2 0.7%	1 0.4%	3 0.5%
Progesterone Receptor (PgR); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Positive	167 58.6%	168 60.2%	335 59.4%
	Negative	118 41.4%	109 39.1%	227 40.2%
	Unknown	0 0.0%	2 0.7%	2 0.4%
Estrogen and progesterone receptor; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	ER and PgR negative	63 22.1%	67 24.0%	130 23.0%
	ER or PgR positive	221 77.5%	212 76.0%	433 76.8%
	ER and PR unknown or negative	1 0.4%	0 0.0%	1 0.2%
Electrocardiogram (ECG) result; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Normal	243 85.3%	246 88.2%	489 86.7%
	Abnormal	39 13.7%	30 10.8%	69 12.2%
	Not performed	3 1.1%	3 1.1%	6 1.1%
Method for brain imaging [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	CT	18 6.3%	19 6.8%	37 6.6%
	MRI	3 1.1%	2 0.7%	5 0.9%
	No brain CT/MRI	264 92.6%	258 92.5%	522 92.6%
		[1] Measure Description: No brain CT or MRI was required if the patient did not show signs/symptoms of central nervous system (CNS) involvement or other unexplained neurological symptoms.
Result of brain CT/MRI [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	No metastasis	21 7.4%	21 7.5%	42 7.4%
	No brain CT/MRI	264 92.6%	258 92.5%	522 92.6%
		[1] Measure Description: No brain CT or MRI was required if the patient did not show signs/symptoms suggestive of CNS involvement or other unexplained neurological symptoms.
Stage at primary diagnosis: Primary tumor (T) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Tis	1 0.4%	2 0.7%	3 0.5%
	T1	66 23.2%	72 25.8%	138 24.5%
	T2	130 45.6%	118 42.3%	248 44.0%
	T3	26 9.1%	32 11.5%	58 10.3%
	T4	45 15.8%	38 13.6%	83 14.7%
	TX	16 5.6%	16 5.7%	32 5.7%
	Missing	1 0.4%	1 0.4%	2 0.4%
		[1] Measure Description: Tis - Ductal carcinoma in situ, TX - Primary Tumor cannot be assessed, T1 - Tumor ≤ 20 mm in greatest dimension, T2 - Tumor > 20 mm but ≤ 50 mm in greatest dimension, T3 - Tumor > 50 mm in greatest dimension, T4 - Tumor of any size with direct extension to chest wall and/or to skin (ulceration or macroscopic nodules).
Stage at primary diagnosis: Regional lymph nodes (N) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	N0	78 27.4%	62 22.2%	140 24.8%
	N1	97 34.0%	116 41.6%	213 37.8%
	N2	55 19.3%	51 18.3%	106 18.8%
	N3	26 9.1%	22 7.9%	48 8.5%
	NX	28 9.8%	27 9.7%	55 9.8%
	Missing	1 0.4%	1 0.4%	2 0.4%
		[1] Measure Description: Nx - Regional lymph nodes cannot be assessed, N0 - No regional lymph node metastases, N1 - Metastases to movable ipsilateral level I, II axillary lymph nodes, N2 - Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted; or in clinically detected ipsilateral internal mammary nodes in absence of clinically evident axillary lymph node metastases, N3 - Metastases in ipsilateral infraclavicular (level III axillary) lymph nodes with or without level I, II axillary lymph node involvement.
Stage at primary diagnosis: Distant metastasis (M) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	M0	222 77.9%	219 78.5%	441 78.2%
	M1	62 21.8%	59 21.1%	121 21.5%
	Missing	1 0.4%	1 0.4%	2 0.4%
		[1] Measure Description: M0 - No clinical or radiographic evidence of distant metastases, M1 - Distant metastases detected, Mx - Metastases cannot be assessed.
Current stage of locally recurrent/ metastatic tumor; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Locally recurrent breast cancer	2 0.7%	0 0.0%	2 0.4%
	Metastatic breast cancer	282 98.9%	279 100.0%	561 99.5%
	Missing	1 0.4%	0 0.0%	1 0.2%
Disease free interval after therapy of primary breast cancer; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Yes	214 75.1%	215 77.1%	429 76.1%
	No	71 24.9%	64 22.9%	135 23.9%
Disease free interval [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	No DFI	71 24.9%	64 22.9%	135 23.9%
	DFI <=12 months	14 4.9%	10 3.6%	24 4.3%
	DFI >12 and <=24 months	52 18.2%	34 12.2%	86 15.2%
	DFI >24 months	148 51.9%	171 61.3%	319 56.6%
		[1] Measure Description: Disease free interval set to 0 months (No DFI), if the patient did not receive previous therapy for primary breast cancer or if the patient was not disease free after previous therapy of primary breast cancer
Metastatic lesions [1]; Measure Type: Count of Participants; Unit of measure: Participants
At least one metastatic lesion	Number Analyzed	285 participants	279 participants	564 participants
		282 98.9%	279 100.0%	561 99.5%
Bone	Number Analyzed	285 participants	279 participants	564 participants
		158 55.4%	151 54.1%	309 54.8%
Lung	Number Analyzed	285 participants	279 participants	564 participants
		112 39.3%	122 43.7%	234 41.5%
Liver	Number Analyzed	285 participants	279 participants	564 participants
		113 39.6%	126 45.2%	239 42.4%
Skin	Number Analyzed	285 participants	279 participants	564 participants
		13 4.6%	9 3.2%	22 3.9%
Soft tissue	Number Analyzed	285 participants	279 participants	564 participants
		69 24.2%	63 22.6%	132 23.4%
Lymph nodes	Number Analyzed	285 participants	279 participants	564 participants
		146 51.2%	171 61.3%	317 56.2%
Other	Number Analyzed	285 participants	279 participants	564 participants
		19 6.7%	25 9.0%	44 7.8%
Lung and / or liver	Number Analyzed	285 participants	279 participants	564 participants
		185 64.9%	203 72.8%	388 68.8%
Soft tissue and/or bone only	Number Analyzed	285 participants	279 participants	564 participants
		41 14.4%	23 8.2%	64 11.3%
		[1] Measure Description: All sites with at least one metastatic lesion. Patients can have multiple sites with metastatic lesions.
Imaging methods; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	CT	270 94.7%	261 93.5%	531 94.1%
	MRI	8 2.8%	12 4.3%	20 3.5%
	X-ray	7 2.5%	6 2.2%	13 2.3%
Target and non-target lesions; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Target lesions only	34 11.9%	22 7.9%	56 9.9%
	Non-target lesions only	65 22.8%	49 17.6%	114 20.2%
	Both	185 64.9%	208 74.6%	393 69.7%
	None	1 0.4%	0 0.0%	1 0.2%
Number of target lesions; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	0 lesions	66 23.2%	49 17.6%	115 20.4%
	1 lesions	48 16.8%	49 17.6%	97 17.2%
	2 lesions	41 14.4%	49 17.6%	90 16.0%
	3 lesions	47 16.5%	39 14.0%	86 15.2%
	4-5 lesions	44 15.4%	57 20.4%	101 17.9%
	>= 6 lesions	39 13.7%	36 12.9%	75 13.3%
Sum of longest diameter of target lesion; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	No lesions	66 23.2%	49 17.6%	115 20.4%
	1-5 cm	86 30.2%	83 29.7%	169 30.0%
	>5-10 cm	64 22.5%	77 27.6%	141 25.0%
	>10 cm	69 24.2%	70 25.1%	139 24.6%
Number of organs with metastases; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	>= 3	105 36.8%	124 44.4%	229 40.6%
	< 3	180 63.2%	155 55.6%	335 59.4%
Previous hormonal therapy [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Neoadjuvant/adjuvant only	113 39.6%	112 40.1%	225 39.9%
	LR/MBC only	25 8.8%	33 11.8%	58 10.3%
	Both	37 13.0%	25 9.0%	62 11.0%
	Other	0 0.0%	1 0.4%	1 0.2%
	None	110 38.6%	108 38.7%	218 38.7%
		[1] Measure Description: LR/MBC = for locally recurrent / metastatic breast cancer
Neoadjuvant/ adjuvant hormonal therapy only [1]; Measure Type: Count of Participants; Unit of measure: Participants
Anti-estrogens	Number Analyzed	113 participants	112 participants	225 participants
		87 77.0%	89 79.5%	176 78.2%
Aromatase inhibitors	Number Analyzed	113 participants	112 participants	225 participants
		56 49.6%	56 50.0%	112 49.8%
LR-RH analogues	Number Analyzed	113 participants	112 participants	225 participants
		12 10.6%	15 13.4%	27 12.0%
Progesterone	Number Analyzed	113 participants	112 participants	225 participants
		0 0.0%	1 0.9%	1 0.4%
Other	Number Analyzed	113 participants	112 participants	225 participants
		0 0.0%	1 0.9%	1 0.4%
		[1] Measure Analysis Population Description: Only participants with neoadjuvant/adjuvant hormonal therapy included. Multiple answers per patient possible.
Hormonal therapy for LR/MBC only [1]; Measure Type: Count of Participants; Unit of measure: Participants
Anti-estrogens	Number Analyzed	25 participants	33 participants	58 participants
		18 72.0%	29 87.9%	47 81.0%
Aromatase inhibitors	Number Analyzed	25 participants	33 participants	58 participants
		17 68.0%	23 69.7%	40 69.0%
LH-RH analogues	Number Analyzed	25 participants	33 participants	58 participants
		1 4.0%	4 12.1%	5 8.6%
		[1] Measure Analysis Population Description: Only participants with hormonal therapy for LR/ MBC included. Multiple answers per patient possible.
Previous neoadjuvant chemotherapy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Anthracycline and taxane	16 5.6%	11 3.9%	27 4.8%
	Anthracycline, no taxane	41 14.4%	33 11.8%	74 13.1%
	Taxane, no anthracycline	5 1.8%	5 1.8%	10 1.8%
	No anthracycline, no taxane, other	2 0.7%	3 1.1%	5 0.9%
	None	221 77.5%	227 81.4%	448 79.4%
Previous adjuvant chemotherapy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	285 participants	279 participants	564 participants
	Anthracycline and taxane	21 7.4%	25 9.0%	46 8.2%
	Anthracycline, no taxane	83 29.1%	89 31.9%	172 30.5%
	Taxane, no anthracycline	16 5.6%	12 4.3%	28 5.0%
	No anthracycline, no taxane, other	30 10.5%	25 9.0%	55 9.8%
	None	135 47.4%	128 45.9%	263 46.6%
Previous neoadjuvant/adjuvant chemotherapy [1]; Measure Type: Count of Participants; Unit of measure: Participants
Anthracycline and taxane	Number Analyzed	285 participants	279 participants	564 participants
		37 13.0%	35 12.5%	72 12.8%
Anthracycline, no taxane	Number Analyzed	285 participants	279 participants	564 participants
		110 38.6%	112 40.1%	222 39.4%
Taxane, no anthracycline	Number Analyzed	285 participants	279 participants	564 participants
		21 7.4%	16 5.7%	37 6.6%
No anthracycline, no taxane, other	Number Analyzed	285 participants	279 participants	564 participants
		32 11.2%	28 10.0%	60 10.6%
None	Number Analyzed	285 participants	279 participants	564 participants
		105 36.8%	103 36.9%	208 36.9%
		[1] Measure Description: Patients for whom their neoadjuvant and adjuvant chemotherapy differed are counted in both the pertinent categories.
Previous neoadjuvant/adjuvant chemotherapy medications [1]; Measure Type: Count of Participants; Unit of measure: Participants
Anthracycline	Number Analyzed	285 participants	279 participants	564 participants
		145 50.9%	144 51.6%	289 51.2%
Taxane	Number Analyzed	285 participants	279 participants	564 participants
		57 20.0%	50 17.9%	107 19.0%
No anthracycline, no taxane, other	Number Analyzed	285 participants	279 participants	564 participants
		26 9.1%	26 9.3%	52 9.2%
None	Number Analyzed	285 participants	279 participants	564 participants
		105 36.8%	103 36.9%	208 36.9%
		[1] Measure Description: Patients who received both anthracycline and taxane in an adjuvant or neoadjuvant chemotherapy are counted in both categories.
Previous radiotherapy [1] [2]; Measure Type: Count of Participants; Unit of measure: Participants
Neoadjuvant	Number Analyzed	191 participants	194 participants	385 participants
		8 4.2%	9 4.6%	17 4.4%
Adjuvant	Number Analyzed	191 participants	194 participants	385 participants
		167 87.4%	171 88.1%	338 87.8%
For relief of metastatic bone pain	Number Analyzed	191 participants	194 participants	385 participants
		32 16.8%	44 22.7%	76 19.7%
		[1] Measure Description: Multiple answers per patient possible. In case of multiple treatments in the same category, the patient is counted only once in that category.; [2] Measure Analysis Population Description: Restricted to patients with previous radiotherapy.
Previous surgery [1] [2]; Measure Type: Count of Participants; Unit of measure: Participants
Total mastectomy	Number Analyzed	241 participants	239 participants	480 participants
		131 54.4%	135 56.5%	266 55.4%
Breast conserving surgery	Number Analyzed	241 participants	239 participants	480 participants
		111 46.1%	99 41.4%	210 43.8%
Biopsy/Aspiration	Number Analyzed	241 participants	239 participants	480 participants
		54 22.4%	48 20.1%	102 21.3%
Other	Number Analyzed	241 participants	239 participants	480 participants
		35 14.5%	29 12.1%	64 13.3%
		[1] Measure Description: Multiple answers per patient possible. In case of multiple treatments in the same category, the patient is counted only once in that category.; [2] Measure Analysis Population Description: Restricted to patients with previous surgery.
Height; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	285 participants	279 participants	564 participants
		162 (6.60)	162.3 (6.48)	162.2 (6.54)
Body Surface Area (BSA); Mean (Standard Deviation); Unit of measure: M²
	Number Analyzed	285 participants	279 participants	564 participants
		1.76 (0.1834)	1.773 (0.1688)	1.767 (0.1763)
Systolic blood pressure; Mean (Standard Deviation); Unit of measure: mmHg
	Number Analyzed	285 participants	279 participants	564 participants
		127.9 (12.91)	128.7 (13.85)	128.3 (13.38)
Diastolic blood pressure; Mean (Standard Deviation); Unit of measure: mmHg
	Number Analyzed	285 participants	279 participants	564 participants
		78.1 (8.23)	77.9 (9.34)	78.0 (8.79)
Heart rate; Mean (Standard Deviation); Unit of measure: Bpm
	Number Analyzed	285 participants	279 participants	564 participants
		79.7 (11.27)	79.1 (11.41)	79.4 (11.33)
Body temperature; Mean (Standard Deviation); Unit of measure: °C
	Number Analyzed	285 participants	279 participants	564 participants
		36.55 (0.265)	36.47 (0.305)	36.51 (0.288)
Left Ventricular Ejection Fraction (LVEF); Mean (Standard Deviation); Unit of measure: Percentage of ejected blood
	Number Analyzed	285 participants	279 participants	564 participants
		63.4 (5.32)	62.6 (6.26)	63.0 (5.81)
Time since diagnosis of adenocarcinoma [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	285 participants	279 participants	564 participants
		55.2 (56.46)	58.9 (55.09)	57.0 (55.77)
		[1] Measure Description: Histologically or cytologically confirmed adenocarcinoma.
Time since diagnosis of LR or MT [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	285 participants	279 participants	564 participants
		5.7 (14.77)	7.6 (19.11)	6.7 (17.07)
		[1] Measure Description: LR or MT = Locally recurrent or metastatic tumor.
Disease free interval [1]; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	285 participants	279 participants	564 participants
		43.6 (48.84)	48.0 (48.53)	45.8 (48.70)
		[1] Measure Description: Disease free interval was set to 0 months (No DFI) if the patient did not receive previous therapy for primary breast cancer or the patient was not disease free after previous therapy for primary breast cancer.
Number of target lesions; Mean (Standard Deviation); Unit of measure: Number of lesions
	Number Analyzed	285 participants	279 participants	564 participants
		2.7 (2.52)	2.8 (2.42)	2.7 (2.47)
Sum of longest diameter of target lesions; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	285 participants	279 participants	564 participants
		6.758 (7.4372)	6.872 (6.6679)	6.815 (7.0610)
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	285 participants	279 participants	564 participants
		71.97 (15.679)	72.90 (14.350)	72.43 (15.030)

Outcome Measures

1. Primary Outcome

Title	Overall Survival (PP Population)
Description	Overall survival (OS) defined as time from randomization to date of death from any cause. Patients without recorded death were censored at the date the patient was last known to be alive. OS was analyzed at two looks, one interim look and the final analysis. Due to group sequential testing, the overall significance level alpha = 0.025 was spent on both looks according to Lan-DeMets spending method with O'Brien-Fleming-type boundaries. Alpha spent at Interim after 47% of information was 0.0010. Alpha spent at final analysis after 99% of information was 0.0250.
Time Frame	Time from the date of randomization to the date of death or date last known to be alive, assessed up to approximately 6 years

Outcome Measure Data

Analysis Population Description

Per Protocol Population (PP)

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	266	265
Median (95% Confidence Interval); Unit of Measure: months
	30.2; (25.6 to 32.6)	26.1; (22.3 to 29.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab plus Capecitabine vs. Bevacizumab plus Paclitaxel for OS (interim, stratified).
	Type of Statistical Test	Non-Inferiority
	Comments	Null hypothesis: Hazard Ratio (HR) >= 1.33 Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
Statistical Test of Hypothesis	P-Value	0.1983
	Comments	Based on approach using repeated confidence intervals, with one-sided 97.5% repeated confidence intervals
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.042
	Confidence Interval	(1-Sided) 97.5%; 1.689
	Estimation Comments	HR is the hazard rate of Bevacizumab plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for OS (final, stratified).
	Type of Statistical Test	Non-Inferiority
	Comments	Null hypothesis: Hazard Ratio (HR) >= 1.33 Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
Statistical Test of Hypothesis	P-Value	0.0070
	Comments	Based on approach using repeated confidence intervals, with one-sided 97.5% repeated confidence intervals. Non-inferiority margin was a HR of 1.33.
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.018
	Confidence Interval	(1-Sided) 97.5%; 1.261
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for OS (interim, unstratified).
	Type of Statistical Test	Non-Inferiority
	Comments	Null hypothesis: Hazard Ratio (HR) >= 1.33 Based on Cox proportional hazards model.
Statistical Test of Hypothesis	P-Value	0.2024
	Comments	Based on approach using repeated confidence intervals, with one-sided 97.5% repeated confidence intervals. Non-inferiority margin was a HR of 1.33.
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.058
	Confidence Interval	(1-Sided) 97.5%; 1.674
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for OS (final, unstratified).
	Type of Statistical Test	Non-Inferiority
	Comments	Null hypothesis: Hazard Ratio (HR) >= 1.33 Based on Cox proportional hazards model.
Statistical Test of Hypothesis	P-Value	0.0612
	Comments	Based on approach using repeated confidence intervals, with one-sided 97.5% repeated confidence intervals. Non-inferiority margin was a HR of 1.33.
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.134
	Confidence Interval	(1-Sided) 97.5%; 1.386
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

2. Primary Outcome

Title	Overall Survival (ITT Population)
Description	Overall survival (OS) defined as time from randomization to date of death from any cause. Patients without recorded death were censored at the date the patient was last known to be alive. OS was analyzed at two looks, one interim look and the final analysis. Due to group sequential testing, the overall significance level alpha = 0.025 was spent on both looks according to Lan-DeMets spending method with O'Brien-Fleming-type boundaries. Alpha spent at Interim after 50% of information was 0.0014. Alpha spent at final analysis after 99% of information was 0.0250.
Time Frame	Time from the date of randomization to the date of death or date last known to be alive, assessed up to approximately 6 years

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population (ITT)

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	285	279
Median (95% Confidence Interval); Unit of Measure: months
	29.5; (25.3 to 32.4)	26.0; (22.3 to 29.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for OS (interim, stratified).
	Type of Statistical Test	Non-Inferiority
	Comments	Null hypothesis: Hazard ratio (HR) >= 1.33 Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
Statistical Test of Hypothesis	P-Value	0.1534
	Comments	Based on approach using repeated confidence intervals, with one-sided 97.5% repeated confidence intervals
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.027
	Confidence Interval	(1-Sided) 97.5%; 1.606
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for OS (final, stratified).
	Type of Statistical Test	Non-Inferiority
	Comments	Null hypothesis: Hazard ratio (HR) >= 1.33 Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
Statistical Test of Hypothesis	P-Value	0.0085
	Comments	Based on approach using repeated confidence intervals, with one-sided 97.5% repeated confidence intervals
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.035
	Confidence Interval	(1-Sided) 97.5%; 1.273
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for OS (interim, unstratified).
	Type of Statistical Test	Non-Inferiority
	Comments	Null hypothesis: Hazard Ratio (HR) >= 1.33 Based on Cox proportional hazards model.
Statistical Test of Hypothesis	P-Value	0.1778
	Comments	Based on approach using repeated confidence intervals, with one-sided 97.5% repeated confidence intervals
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.058
	Confidence Interval	(1-Sided) 97.5%; 1.623
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for OS (final, unstratified).
	Type of Statistical Test	Non-Inferiority
	Comments	Null hypothesis: Hazard Ratio (HR) >= 1.33 Based on Cox proportional hazards model.
Statistical Test of Hypothesis	P-Value	0.049
	Comments	Based on approach using repeated confidence intervals, with one-sided 97.5% repeated confidence intervals
	Method	Regression, Cox
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.126
	Confidence Interval	(1-Sided) 97.5%; 1.37
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

3. Secondary Outcome

Title	Observation Time (ITT Population)
Description	Median observation time estimated with reverse Kaplan-Meier methods. Observation time (in months) is defined as time from randomization to the day the patient was last confirmed to be alive. In case of patient deaths the time was censored at the day of death.
Time Frame	Up to approximately 6 years

Outcome Measure Data

Analysis Population Description

Intention-to-Treat population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	285	279
Median (95% Confidence Interval); Unit of Measure: months
	54.3; (53.1 to 57.5)	55.7; (53.7 to 58.1)

4. Secondary Outcome

Title	Best Overall Response (ITT Population)
Description	The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Time Frame	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	285	279
Measure Type: Count of Participants; Unit of Measure: Participants
Complete response	10 3.5%	2 0.7%
Partial response	115 40.4%	74 26.5%
Stable disease	127 44.6%	138 49.5%
Progressive disease	18 6.3%	47 16.8%
Not evaluable	15 5.3%	18 6.5%

5. Secondary Outcome

Title	Best Overall Response (PP Population)
Description	The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Time Frame	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	266	265
Measure Type: Count of Participants; Unit of Measure: Participants
Complete response	10 3.8%	2 0.8%
Partial response	111 41.7%	72 27.2%
Stable disease	117 44.0%	130 49.1%
Progressive disease	17 6.4%	45 17.0%
Not evaluable	11 4.1%	16 6.0%

6. Secondary Outcome

Title	Unconfirmed Best Overall Response (ITT Population)
Description	The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment.
Time Frame	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	285	279
Measure Type: Count of Participants; Unit of Measure: Participants
Complete response	16 5.6%	4 1.4%
Partial response	147 51.6%	101 36.2%
Stable disease	89 31.2%	109 39.1%
Progressive disease	18 6.3%	47 16.8%
Not evaluable	15 5.3%	18 6.5%

7. Secondary Outcome

Title	Unconfirmed Best Overall Response (PP Population)
Description	The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment.
Time Frame	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

PP population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	266	265
Measure Type: Count of Participants; Unit of Measure: Participants
Complete response	16 6.0%	4 1.5%
Partial response	141 53.0%	96 36.2%
Stable disease	81 30.5%	104 39.2%
Progressive disease	17 6.4%	45 17.0%
Not evaluable	11 4.1%	16 6.0%

8. Secondary Outcome

Title	Objective Response Rate and Disease Control Rate (ITT Population)
Description	Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Time Frame	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	285	279
Measure Type: Count of Participants; Unit of Measure: Participants
Objective response	125 43.9%	76 27.2%
Disease control	252 88.4%	214 76.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	Odds Ratio (OR) of objective response and Cochran-Mantel-Haenszel (CMH) test (stratified)
	Type of Statistical Test	Superiority
	Comments	OR is the odds for objective response of Bevacizumab Plus Capecitabine divided by the odds for objective response of Bevacizumab plus Paclitaxel
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	Test adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; 0.33 to 0.67
	Estimation Comments	OR is the odds for objective response of Bevacizumab Plus Capecitabine divided by the odds for objective response of Bevacizumab plus Paclitaxel

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	Difference in ORR in Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-17
	Confidence Interval	(2-Sided) 95%; -24 to -9
	Estimation Comments	Difference calculated as ORR in Bevacizumab Plus Capecitabine minus ORR in Bevacizumab plus Paclitaxel, units in percent.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	OR of disease control and CMH test (stratified)
	Type of Statistical Test	Superiority
	Comments	OR is the odds for disease control of Bevacizumab Plus Capecitabine divided by the odds for disease control of Bevacizumab plus Paclitaxel
Statistical Test of Hypothesis	P-Value	0.0006
	Comments	Test adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; 0.27 to 0.70
	Estimation Comments	OR is the odds for disease control of Bevacizumab Plus Capecitabine divided by the odds for disease control of Bevacizumab plus Paclitaxel

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	Difference in DCR in Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-12
	Confidence Interval	(2-Sided) 95%; -18 to -6
	Estimation Comments	Difference calculated as the DCR in Bevacizumab Plus Capecitabine minus ORR in Bevacizumab plus Paclitaxel, units in percent.

9. Secondary Outcome

Title	Objective Response Rate and Disease Control Rate (PP Population)
Description	Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase
Time Frame	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

PP population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	266	265
Measure Type: Count of Participants; Unit of Measure: Participants
Objective response	121 45.5%	74 27.9%
Disease control	238 89.5%	204 77.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	OR of objective response and CMH test (stratified)
	Type of Statistical Test	Superiority
	Comments	OR is the odds for objective response of Bevacizumab Plus Capecitabine divided by the odds for objective response of Bevacizumab plus Paclitaxel
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	Test adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.45
	Confidence Interval	(2-Sided) 95%; 0.31 to 0.65
	Estimation Comments	OR is the odds for objective response of Bevacizumab Plus Capecitabine divided by the odds for objective response of Bevacizumab plus Paclitaxel

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	Difference in ORR in Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-18
	Confidence Interval	(2-Sided) 95%; -26 to -10
	Estimation Comments	Difference calculated as ORR in Bevacizumab Plus Capecitabine minus ORR in Bevacizumab plus Paclitaxel, units in percent.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	OR of disease control and CMH test (stratified)
	Type of Statistical Test	Superiority
	Comments	OR is the odds for disease control of Bevacizumab Plus Capecitabine divided by the odds for disease control of Bevacizumab plus Paclitaxel
Statistical Test of Hypothesis	P-Value	0.0003
	Comments	Test adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.65
	Estimation Comments	OR is the odds for disease control of Bevacizumab Plus Capecitabine divided by the odds for disease control of Bevacizumab plus Paclitaxel

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	Difference in DCR in Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-12
	Confidence Interval	(2-Sided) 95%; -19 to -6
	Estimation Comments	Difference calculated as the DCR in Bevacizumab Plus Capecitabine minus ORR in Bevacizumab plus Paclitaxel, units in percent.

10. Secondary Outcome

Title	Unconfirmed Objective Response Rate and Disease Control Rate (ITT Population)
Description	Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment.
Time Frame	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	285	279
Measure Type: Count of Participants; Unit of Measure: Participants
Objective response	163 57.2%	105 37.6%
Disease control	252 88.4%	214 76.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	OR of objective response and CMH test (stratified)
	Type of Statistical Test	Superiority
	Comments	OR is the odds for objective response of Bevacizumab Plus Capecitabine divided by the odds for objective response of Bevacizumab plus Paclitaxel
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	Test adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; 0.31 to 0.63
	Estimation Comments	OR is the odds for objective response of Bevacizumab Plus Capecitabine divided by the odds for objective response of Bevacizumab plus Paclitaxel

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	Difference in ORR in Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-20
	Confidence Interval	(2-Sided) 95%; -28 to -11
	Estimation Comments	Difference calculated as ORR in Bevacizumab Plus Capecitabine minus ORR in Bevacizumab plus Paclitaxel, units in percent.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	OR of disease control and CMH test (stratified)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0006
	Comments	Test adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.43
	Confidence Interval	(2-Sided) 95%; 0.27 to 0.70
	Estimation Comments	OR is the odds for disease control of Bevacizumab Plus Capecitabine divided by the odds for disease control of Bevacizumab plus Paclitaxel

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	Difference in DCR in Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-12
	Confidence Interval	(2-Sided) 95%; -18 to -6
	Estimation Comments	Difference calculated as DCR in Bevacizumab Plus Capecitabine minus DCR in Bevacizumab plus Paclitaxel, units in percent.

11. Secondary Outcome

Title	Unconfirmed Objective Response Rate and Disease Control Rate (PP Population)
Description	Objective response rate (ORR) is defined as the proportion of patients with complete response or partial response. Disease control rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease. The best overall response according to the RECIST criteria is the best response recorded from the start of the treatment until disease progression/recurrence or within 28 days of last intake of study medication in the Study Treatment Phase. Complete and partial response in this summary did not require a confirmation by a second tumor assessment
Time Frame	Up to disease progression or up to 28 days after last intake of study medication, assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

PP population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	266	265
Measure Type: Count of Participants; Unit of Measure: Participants
Objective response	157 59.0%	100 37.7%
Disease control	238 89.5%	204 77.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	OR of objective response and CMH test (stratified)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	Test adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.42
	Confidence Interval	(2-Sided) 95%; 0.29 to 0.60
	Estimation Comments	OR is the odds for objective response of Bevacizumab Plus Capecitabine divided by the odds for objective response of Bevacizumab plus Paclitaxel

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	Difference in ORR in Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-21
	Confidence Interval	(2-Sided) 95%; -30 to -13
	Estimation Comments	Difference calculated as ORR in Bevacizumab Plus Capecitabine minus ORR in Bevacizumab plus Paclitaxel, unit in percent.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	OR of disease control and CMH test (stratified)
	Type of Statistical Test	Superiority
	Comments	OR is the odds for disease control of Bevacizumab Plus Capecitabine divided by the odds for disease control of Bevacizumab plus Paclitaxel
Statistical Test of Hypothesis	P-Value	0.0003
	Comments	Test adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.65
	Estimation Comments	OR is the odds for disease control of Bevacizumab Plus Capecitabine divided by the odds for disease control of Bevacizumab plus Paclitaxel

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	Difference in DCR in Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-12
	Confidence Interval	(2-Sided) 95%; -19 to -6
	Estimation Comments	Difference calculated as DCR in Bevacizumab Plus Capecitabine minus DCR in Bevacizumab plus Paclitaxel, unit in percent.

12. Secondary Outcome

Title	Progression Free Survival (ITT Population)
Description	Progression Free Survival (PFS) is defined as time from randomization to date of documented progression or date of death due to any cause, whichever occurred first. Patients without recorded progression or death were censored at the last date they were known to have not progressed. Patients who were randomized and had no post-baseline tumor assessment were censored on the day of randomization. Median PFS, associated stratified Hazard Ratio (HR).
Time Frame	Time from the date of randomization to disease progression, death or censoring (whichever occurred first), assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	285	279
Median (95% Confidence Interval); Unit of Measure: months
	10.9; (10.3 to 12.9)	8.1; (6.8 to 8.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for PFS (stratified) Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
	Type of Statistical Test	Superiority
	Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.
Statistical Test of Hypothesis	P-Value	0.0066
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Two-sided log-rank test adjusted by stratification factors at randomization
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.61
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

13. Secondary Outcome

Title	Progression Free Survival (PP Population)
Description	Progression Free Survival (PFS) is defined as time from randomization to date of documented progression or date of death due to any cause, whichever occurred first. Patients without recorded progression or death were censored at the last date they were known to have not progressed. Patients who were randomized and had no post-baseline tumor assessment were censored on the day of randomization. Median PFS, associated stratified Hazard Ratio (HR).
Time Frame	Time from the date of randomization to disease progression, death or censoring (whichever occurred first), assessed up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

PP population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	266	265
Median (95% Confidence Interval); Unit of Measure: months
	10.9; (10.3 to 12.9)	8.2; (7.1 to 9.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab plus Capecitabine vs. Bevacizumab plus Paclitaxel for PFS (stratified) Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
	Type of Statistical Test	Superiority
	Comments	HR is the hazard rate of Bevacizumab plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.
Statistical Test of Hypothesis	P-Value	0.0094
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Two-sided log-rank test adjusted by stratification factors at randomization
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 1.07 to 1.61
	Estimation Comments	HR is the hazard rate of Bevacizumab plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

14. Secondary Outcome

Title	Time to Treatment Failure (ITT Population)
Description	Time to treatment failure (TTF) was defined as time from first drug intake to progression, death or withdrawal from study treatment, whichever occurred first. Patients without an event were censored at the date of the last tumor assessment or last treatment administration, whichever occurred last. Median TTF, associated stratified Hazard Ratio (HR).
Time Frame	From first drug intake to progression, death or withdrawal from study treatment or study closure (whichever occurred first), assessed up to approximately 4.5 years

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	285	279
Median (95% Confidence Interval); Unit of Measure: months
	8.4; (8.0 to 9.7)	7.2; (6.0 to 8.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab plus Capecitabine vs. Bevacizumab plus Paclitaxel for TTF (stratified) Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
	Type of Statistical Test	Superiority
	Comments	HR is the hazard rate of Bevacizumab plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.
Statistical Test of Hypothesis	P-Value	0.1957
	Comments	Two-sided log-rank test adjusted by stratification factors at randomization
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.35
	Estimation Comments	HR is the hazard rate of Bevacizumab plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

15. Secondary Outcome

Title	Time to Treatment Failure (PP Population)
Description	Time to treatment failure (TTF) was defined as time from first drug intake to progression, death or withdrawal from study treatment, whichever occurred first. Patients without an event were censored at the date of the last tumor assessment or last treatment administration, whichever occurred last. Median TTF, associated stratified Hazard Ratio (HR).
Time Frame	From first drug intake to progression, death or withdrawal from study treatment or study closure (whichever occurred first), assessed up to approximately 4.5 years

Outcome Measure Data

Analysis Population Description

PP population

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	266	265
Median (95% Confidence Interval); Unit of Measure: months
	8.3; (8.0 to 9.4)	7.3; (5.9 to 8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab plus Capecitabine vs. Bevacizumab plus Paclitaxel for TTF (stratified) Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
	Type of Statistical Test	Superiority
	Comments	HR is the hazard rate of Bevacizumab plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.
Statistical Test of Hypothesis	P-Value	0.2583
	Comments	Two-sided log-rank test adjusted by stratification factors at randomization
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.34
	Estimation Comments	HR is the hazard rate of Bevacizumab plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

16. Secondary Outcome

Title	Time to Response (ITT Population)
Description	Time to response (TR) was defined as time from randomization until occurrence of response (complete response (CR) or partial response (PR)) according to RECIST criteria. Patients without response were censored after the longest time to response observed in any patient. Median TR, associated stratified Hazard Ratio (HR). Since the median TR was not observed, the number of subjects with a response at given timepoints were reported.
Time Frame	Time from randomization until occurrence of response, assessed up 1.7 years

Outcome Measure Data

Analysis Population Description

ITT population, median not reached

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	285	279
Measure Type: Count of Participants; Unit of Measure: Participants
Month 3	83 29.1%	57 20.4%
Month 6	111 38.9%	69 24.7%
Month 9	121 42.5%	74 26.5%
Month 12	123 43.2%	75 26.9%
Month 15	123 43.2%	75 26.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for TR (stratified) Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
	Type of Statistical Test	Superiority
	Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.
Statistical Test of Hypothesis	P-Value	0.0001
	Comments	Two-sided log-rank test adjusted by stratification factors at randomization
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; 0.43 to 0.77
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

17. Secondary Outcome

Title	Time to Response (PP Population)
Description	Time to response (TR) was defined as time from randomization until occurrence of response (complete response (CR) or partial response (PR)) according to RECIST criteria. Patients without response were censored after the longest time to response observed in any patient. Median TR, associated stratified Hazard Ratio (HR). Since the median TR was not observed, the number of subjects with a response at given timepoints were reported.
Time Frame	Time from randomization until occurrence of response, assessed up 1.7 years

Outcome Measure Data

Analysis Population Description

PP population, median not reached

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	266	265
Measure Type: Count of Participants; Unit of Measure: Participants
Month 3	81 30.5%	56 21.1%
Month 6	108 40.6%	68 25.7%
Month 9	118 44.4%	72 27.2%
Month 12	119 44.7%	73 27.5%
Month 15	119 44.7%	73 27.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for TR (stratified) Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
	Type of Statistical Test	Superiority
	Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.
Statistical Test of Hypothesis	P-Value	0.0001
	Comments	Two-sided log-rank test adjusted by stratification factors at randomization
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; 0.41 to 0.75
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

18. Secondary Outcome

Title	Duration of Response (ITT Population)
Description	Duration of response (DR) was defined as time from date of first occurrence of any response (complete response (CR) or partial response (PR)) until the occurrence of progression of disease or death. Patients with response who neither progressed nor died were censored at the date of their last tumor assessment. Median DR, associated stratified Hazard Ratio (HR).
Time Frame	Time from first occurrence of CR or PR until disease progression, death or study closure, whichever occurred first, assessed up to 3.4 years after occurrence of response.

Outcome Measure Data

Analysis Population Description

ITT population restricted to patients who experienced a partial or complete response

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	125	76
Median (95% Confidence Interval); Unit of Measure: months
	11.2; (10.1 to 14.0)	10.3; (8.6 to 12.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Bevacizumab Plus Capecitabine vs. Bevacizumab plus Paclitaxel for DR (stratified) Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
	Type of Statistical Test	Superiority
	Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.
Statistical Test of Hypothesis	P-Value	0.0582
	Comments	Two-sided log-rank test adjusted by stratification factors at randomization
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; 0.99 to 2.02
	Estimation Comments	HR is the hazard rate of Bevacizumab Plus Capecitabine divided by hazard rate of Bevacizumab plus Paclitaxel.

19. Secondary Outcome

Title	Duration of Response (PP Population)
Description	Duration of response (DR) was defined as time from date of first occurrence of any response (complete response (CR) or partial response (PR)) until the occurrence of progression of disease or death. Patients with response who neither progressed nor died were censored at the date of their last tumor assessment. Median DR, associated stratified Hazard Ratio (HR).
Time Frame	Time from first occurrence of CR or PR until disease progression, death or study closure, whichever occurred first, assessed up to 3.4 years after occurrence of response.

Outcome Measure Data

Analysis Population Description

PP population restricted to patients who experienced a partial or complete response

Arm/Group Title	Bevacizumab Plus Paclitaxel	Bevacizumab Plus Capecitabine
Arm/Group Description:	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks	Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
Overall Number of Participants Analyzed	121	74
Median (95% Confidence Interval); Unit of Measure: months
	11.2; (9.5 to 14.2)	10.3; (8.4 to 12.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab Plus Paclitaxel, Bevacizumab Plus Capecitabine
	Comments	HR of Arm B vs. Arm A for DR (stratified) Based on Cox proportional hazards model adjusted by stratification factors at randomization: estrogen and/or progesterone status (positive vs. other); country; menopausal status (premenopausal or male <=50 years of age vs. postmenopausal or male >50 years of age)
	Type of Statistical Test	Superiority
	Comments	HR is the hazard rate of Arm B divided by hazard rate of Arm A.
Statistical Test of Hypothesis	P-Value	0.0429
	Comments	Two-sided log-rank test adjusted by stratification factors at randomization
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 1.01 to 2.10
	Estimation Comments	HR is the hazard rate of Arm B divided by hazard rate of Arm A.

Adverse Events

Time Frame	From start of study drug administration until 28 days after the last dose of study medication, assessed up to approximately 5 years
Adverse Event Reporting Description	The safety population comprised all patients randomized who received at least one dose of study medication. For the purpose of safety analyses, patients were included in the treatment groups of the treatment actually received. However, if patients received only one component of the assigned combination treatment (e.g. only paclitaxel in group A), then they were analyzed under the Treatment group randomized. 1 patient in Arm A and 2 patients in Arm B were not treated.
Arm/Group Title	Bevacizumab Plus Paclitaxel		Bevacizumab Plus Capecitabine
Arm/Group Description	Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks		Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks
All-Cause Mortality
	Bevacizumab Plus Paclitaxel		Bevacizumab Plus Capecitabine
	Affected / at Risk (%)		Affected / at Risk (%)
Total	196/284 (69.01%)		209/277 (75.45%)
Serious Adverse Events
	Bevacizumab Plus Paclitaxel		Bevacizumab Plus Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/284 (22.89%)		68/277 (24.55%)
Blood and lymphatic system disorders
Anaemia † 1	0/284 (0.00%)	0	4/277 (1.44%)	5
Febrile neutropenia † 1	2/284 (0.70%)	2	1/277 (0.36%)	1
Leukopenia † 1	1/284 (0.35%)	1	1/277 (0.36%)	1
Neutropenia † 1	1/284 (0.35%)	1	1/277 (0.36%)	1
Cardiac disorders
Acute coronary syndrome † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Acute myocardial infarction † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Atrial fibrillation † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Atrioventricular block † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Atrioventricular block complete † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Cardio-respiratory arrest † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Cardiopulmonary failure † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Systolic dysfunction † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/284 (0.00%)	0	2/277 (0.72%)	2
Abdominal pain upper † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Ascites † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Constipation † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Diarrhoea † 1	1/284 (0.35%)	1	4/277 (1.44%)	4
Dyspepsia † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Dysphagia † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Gastric ulcer † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Ileus † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Intestinal obstruction † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Intestinal perforation † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Melaena † 1	1/284 (0.35%)	1	1/277 (0.36%)	1
Nausea † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Oesophageal stenosis † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Stomatitis † 1	0/284 (0.00%)	0	2/277 (0.72%)	2
Upper gastrointestinal haemorrhage † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Vomiting † 1	0/284 (0.00%)	0	2/277 (0.72%)	3
General disorders
Catheter site pain † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Chest pain † 1	1/284 (0.35%)	1	1/277 (0.36%)	1
Death † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Fatigue † 1	2/284 (0.70%)	2	1/277 (0.36%)	1
Gait disturbance † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
General physical health deterioration † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Generalised oedema † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Pain † 1	1/284 (0.35%)	1	1/277 (0.36%)	1
Pyrexia † 1	3/284 (1.06%)	3	0/277 (0.00%)	0
Hepatobiliary disorders
Acute hepatic failure † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Cholangitis † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Cholecystitis acute † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Cholelithiasis † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Hepatic function abnormal † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Immune system disorders
Drug hypersensitivity † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Hypersensitivity † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Infections and infestations
Abscess limb † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Atypical pneumonia † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Catheter site infection † 1	3/284 (1.06%)	3	0/277 (0.00%)	0
Cellulitis † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Erysipelas † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Herpes zoster † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Lung infection † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Pneumonia † 1	3/284 (1.06%)	4	0/277 (0.00%)	0
Skin infection † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Tooth abscess † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Upper respiratory tract infection † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Injury, poisoning and procedural complications
Fracture † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Hip fracture † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Toxicity to various agents † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Investigations
Gamma-glutamyltransferase increased † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Hepatic enzyme increased † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Metabolism and nutrition disorders
Electrolyte imbalance † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Hypercalcaemia † 1	0/284 (0.00%)	0	2/277 (0.72%)	3
Hyperglycaemia † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Hyponatraemia † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Bone pain † 1	0/284 (0.00%)	0	2/277 (0.72%)	2
Osteonecrosis of jaw † 1	2/284 (0.70%)	2	0/277 (0.00%)	0
Pain in extremity † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Pathological fracture † 1	1/284 (0.35%)	1	3/277 (1.08%)	3
Spinal osteoarthritis † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Nervous system disorders
Brain hypoxia † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Brain oedema † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Cerebral ischaemia † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Cerebrovascular accident † 1	1/284 (0.35%)	1	1/277 (0.36%)	1
Convulsion † 1	0/284 (0.00%)	0	1/277 (0.36%)	2
Dizziness † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Headache † 1	2/284 (0.70%)	2	2/277 (0.72%)	2
Ischaemic stroke † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Nerve root compression † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Peripheral motor neuropathy † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Peripheral sensory neuropathy † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Syncope † 1	1/284 (0.35%)	1	2/277 (0.72%)	2
Transient ischaemic attack † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Psychiatric disorders
Confusional state † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Depression † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Hallucination, olfactory † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Schizoaffective disorder † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Renal and urinary disorders
Renal colic † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Reproductive system and breast disorders
Endometrial hyperplasia † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	2/284 (0.70%)	2	6/277 (2.17%)	6
Epistaxis † 1	2/284 (0.70%)	3	0/277 (0.00%)	0
Interstitial lung disease † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Pleural effusion † 1	0/284 (0.00%)	0	3/277 (1.08%)	3
Pneumothorax † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Pneumothorax spontaneous † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Pulmonary embolism † 1	2/284 (0.70%)	2	4/277 (1.44%)	4
Respiratory failure † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Skin and subcutaneous tissue disorders
Dermatitis bullous † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Palmar-plantar erythrodysaesthesia syndrome † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Rash † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Skin ulcer † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Surgical and medical procedures
Breast lump removal † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Catheterisation venous † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Tooth extraction † 1	2/284 (0.70%)	2	1/277 (0.36%)	1
Vascular disorders
Aortic thrombosis † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Deep vein thrombosis † 1	1/284 (0.35%)	1	5/277 (1.81%)	5
Haemorrhage † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Hypertension † 1	1/284 (0.35%)	1	2/277 (0.72%)	2
Hypertensive crisis † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Hypovolaemic shock † 1	1/284 (0.35%)	1	0/277 (0.00%)	0
Peripheral ischaemia † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
Thrombosis † 1	0/284 (0.00%)	0	1/277 (0.36%)	1
1 Term from vocabulary, MedDRA (15.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bevacizumab Plus Paclitaxel		Bevacizumab Plus Capecitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	264/284 (92.96%)		240/277 (86.64%)
Blood and lymphatic system disorders
Anaemia † 1	35/284 (12.32%)	59	17/277 (6.14%)	20
Leukopenia † 1	46/284 (16.20%)	127	6/277 (2.17%)	8
Neutropenia † 1	87/284 (30.63%)	204	13/277 (4.69%)	24
Thrombocytopenia † 1	9/284 (3.17%)	12	19/277 (6.86%)	26
Gastrointestinal disorders
Abdominal pain † 1	20/284 (7.04%)	26	18/277 (6.50%)	21
Abdominal pain upper † 1	18/284 (6.34%)	24	14/277 (5.05%)	17
Constipation † 1	27/284 (9.51%)	32	25/277 (9.03%)	32
Diarrhoea † 1	58/284 (20.42%)	83	59/277 (21.30%)	83
Dyspepsia † 1	17/284 (5.99%)	24	15/277 (5.42%)	17
Nausea † 1	57/284 (20.07%)	82	70/277 (25.27%)	94
Stomatitis † 1	22/284 (7.75%)	27	20/277 (7.22%)	24
Vomiting † 1	29/284 (10.21%)	40	34/277 (12.27%)	46
General disorders
Asthenia † 1	44/284 (15.49%)	50	34/277 (12.27%)	37
Fatigue † 1	97/284 (34.15%)	127	76/277 (27.44%)	89
Mucosal inflammation † 1	23/284 (8.10%)	29	13/277 (4.69%)	13
Oedema peripheral † 1	27/284 (9.51%)	28	11/277 (3.97%)	13
Pyrexia † 1	23/284 (8.10%)	27	17/277 (6.14%)	20
Hepatobiliary disorders
Hyperbilirubinaemia † 1	3/284 (1.06%)	3	16/277 (5.78%)	18
Infections and infestations
Urinary tract infection † 1	24/284 (8.45%)	29	14/277 (5.05%)	18
Metabolism and nutrition disorders
Decreased appetite † 1	35/284 (12.32%)	38	33/277 (11.91%)	38
Musculoskeletal and connective tissue disorders
Arthralgia † 1	30/284 (10.56%)	58	18/277 (6.50%)	20
Back pain † 1	27/284 (9.51%)	35	29/277 (10.47%)	29
Bone pain † 1	28/284 (9.86%)	33	29/277 (10.47%)	31
Musculoskeletal pain † 1	3/284 (1.06%)	5	14/277 (5.05%)	15
Myalgia † 1	20/284 (7.04%)	26	9/277 (3.25%)	9
Pain in extremity † 1	25/284 (8.80%)	32	24/277 (8.66%)	28
Nervous system disorders
Dizziness † 1	33/284 (11.62%)	39	17/277 (6.14%)	19
Dysgeusia † 1	17/284 (5.99%)	19	10/277 (3.61%)	14
Headache † 1	37/284 (13.03%)	46	27/277 (9.75%)	32
Neuropathy peripheral † 1	86/284 (30.28%)	105	9/277 (3.25%)	9
Paraesthesia † 1	17/284 (5.99%)	18	12/277 (4.33%)	12
Peripheral sensory neuropathy † 1	23/284 (8.10%)	25	5/277 (1.81%)	5
Polyneuropathy † 1	27/284 (9.51%)	35	6/277 (2.17%)	7
Renal and urinary disorders
Proteinuria † 1	10/284 (3.52%)	13	16/277 (5.78%)	16
Respiratory, thoracic and mediastinal disorders
Cough † 1	32/284 (11.27%)	37	20/277 (7.22%)	22
Dysphonia † 1	35/284 (12.32%)	37	10/277 (3.61%)	11
Dyspnoea † 1	32/284 (11.27%)	39	24/277 (8.66%)	27
Epistaxis † 1	89/284 (31.34%)	122	39/277 (14.08%)	46
Skin and subcutaneous tissue disorders
Alopecia † 1	87/284 (30.63%)	88	5/277 (1.81%)	5
Nail disorder † 1	48/284 (16.90%)	50	10/277 (3.61%)	10
Palmar-plantar erythrodysaesthesia syndrome † 1	8/284 (2.82%)	8	155/277 (55.96%)	197
Rash † 1	17/284 (5.99%)	20	11/277 (3.97%)	14
Vascular disorders
Hypertension † 1	102/284 (35.92%)	192	83/277 (29.96%)	130
1 Term from vocabulary, MedDRA (15.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: MD. Christiane Thallinger
• Organization: CECOG
• Phone: +43 1 409 77 25
• EMail: office@cecog.at

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

Zielinski C, Lang I, Inbar M, Kahan Z, Greil R, Beslija S, Stemmer SM, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Petruzelka L, Eniu A, Nisenbaum B, Dank M, Anghel R, Messinger D, Brodowicz T; TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1230-9. doi: 10.1016/S1470-2045(16)30154-1. Epub 2016 Aug 5.

Brodowicz T, Lang I, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Petruzelka L, Eniu A, Anghel R, Koynov K, Vrbanec D, Pienkowski T, Melichar B, Spanik S, Ahlers S, Messinger D, Inbar MJ, Zielinski C. Selecting first-line bevacizumab-containing therapy for advanced breast cancer: TURANDOT risk factor analyses. Br J Cancer. 2014 Nov 25;111(11):2051-7. doi: 10.1038/bjc.2014.504. Epub 2014 Sep 30.

Lang I, Brodowicz T, Ryvo L, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Messinger D, Zielinski C; Central European Cooperative Oncology Group. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lancet Oncol. 2013 Feb;14(2):125-33. doi: 10.1016/S1470-2045(12)70566-1. Epub 2013 Jan 10.

• Responsible Party: Central European Cooperative Oncology Group
• ClinicalTrials.gov Identifier: NCT00600340
• Other Study ID Numbers: CECOG/BC1.3.005
• First Submitted: January 14, 2008
• First Posted: January 25, 2008
• Results First Submitted: October 22, 2019
• Results First Posted: December 30, 2019
• Last Update Posted: December 30, 2019