Erlotinib Hydrochloride With or Without Bevacizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutations

• ClinicalTrials.gov Identifier: NCT01532089
• Recruitment Status: Completed
• First Posted: February 14, 2012
• Results First Posted: December 26, 2019
• Last Update Posted: October 6, 2020
• Sponsor: Academic and Community Cancer Research United
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Academic and Community Cancer Research United

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Conditions: EGFR Exon 19 Deletion Mutation; EGFR NP_005219.2:p.L858R; Lung Non-Squamous Non-Small Cell Carcinoma; Stage IV Lung Non-Small Cell Cancer AJCC v7
• Interventions: Biological: Bevacizumab; Drug: Erlotinib; Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis
• Enrollment: 88

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm A (Erlotinib Hydrochloride)	Arm B (Erlotinib Hydrochloride, Bevacizumab)
Arm/Group Description	Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Period Title: Overall Study
Started [1]	45	43
Completed	45	43
Not Completed	0	0
[1] Randomized

Baseline Characteristics

Arm/Group Title		Arm A (Erlotinib Hydrochloride)	Arm B (Erlotinib Hydrochloride, Bevacizumab)	Total
Arm/Group Description		Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.	Total of all reporting groups
Overall Number of Baseline Participants		45	43	88
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	45 participants	43 participants	88 participants
		63; (47 to 84)	65; (31 to 84)	63.5; (31 to 84)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants	43 participants	88 participants
	Female	31 68.9%	31 72.1%	62 70.5%
	Male	14 31.1%	12 27.9%	26 29.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants	43 participants	88 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	2 4.4%	1 2.3%	3 3.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	3 6.7%	5 11.6%	8 9.1%
	White	39 86.7%	36 83.7%	75 85.2%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 2.2%	1 2.3%	2 2.3%
ECOG Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants	43 participants	88 participants
	0	19 42.2%	24 55.8%	43 48.9%
	1	26 57.8%	19 44.2%	45 51.1%
		[1] Measure Description: Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.
EGFR exon mutation [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants	43 participants	88 participants
	Exon 19 deletion	30 66.7%	29 67.4%	59 67.0%
	Exon 21 L858R mutation	15 33.3%	14 32.6%	29 33.0%
		[1] Measure Description: Epidermal growth factor receptor (EGFR) exon mutation

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame	Time from randomization to disease progression and death of any cause, whichever comes first, assessed up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Erlotinib Hydrochloride)	Arm B (Erlotinib Hydrochloride, Bevacizumab)
Arm/Group Description:	Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Overall Number of Participants Analyzed	45	43
Median (95% Confidence Interval); Unit of Measure: months
	13.5; (8.8 to 21.6)	17.9; (13.3 to 24.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Erlotinib Hydrochloride), Arm B (Erlotinib Hydrochloride, Bevacizumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.39
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Comparisons of PFS between arms were conducted using a stratified log-rank test.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.50 to 1.31
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame	Time from randomization to death of any causes, assessed up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Erlotinib Hydrochloride)	Arm B (Erlotinib Hydrochloride, Bevacizumab)
Arm/Group Description:	Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Overall Number of Participants Analyzed	45	43
Median (95% Confidence Interval); Unit of Measure: months
	50.6 [1]; (49.4 to NA)	32.4; (26.9 to 54.4)

[1]

The 95% CI upper limit was not reached (insufficient number of participants with events).

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Erlotinib Hydrochloride), Arm B (Erlotinib Hydrochloride, Bevacizumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.33
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; 0.71 to 2.81
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Response Rate (Complete or Partial) to Each Treatment, Evaluated Using the New International Criteria Proposed by the Revised Response Evaluation Criteria in Solid Tumors Guidelines (Version 1.1)
Description	The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites).
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Patients with tumor response data available were included in this analysis.

Arm/Group Title	Arm A (Erlotinib Hydrochloride)	Arm B (Erlotinib Hydrochloride, Bevacizumab)
Arm/Group Description:	Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Overall Number of Participants Analyzed	42	43
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	83; (69 to 93)	81; (67 to 92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Erlotinib Hydrochloride), Arm B (Erlotinib Hydrochloride, Bevacizumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.81
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

4. Secondary Outcome

Title	Progression Free Survival of Patients With Different Mutation Types (Exon Deletion 19 Versus Exon 21 L858R)
Description	Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator by mutation type.
Time Frame	From the date of randomization to the date of disease progression or death of any cause, whichever comes first, assessed up to 6 years

Outcome Measure Data

Analysis Population Description

This analysis includes all patients with EGFR exon mutation data available and primary endpoint data available.

Arm/Group Title	Exon 19 Deletion	Exon 21 L858R
Arm/Group Description:	Patients with exon 19 deletion EGFR exon mutation.	Patients with exon 21 L858R EGFR exon mutation.
Overall Number of Participants Analyzed	59	29
Median (95% Confidence Interval); Unit of Measure: months
	17.9; (13.5 to 23.9)	12.6; (9.0 to 24.1)

5. Secondary Outcome

Title	Number of Patients Experiencing Toxicity
Description	The number of patients experiencing toxicity defined as grade 3 or higher adverse events (using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) considered at least possibly related to treatment is reported below.
Time Frame	Up to 42 days after treatment discontinuation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Erlotinib Hydrochloride)	Arm B (Erlotinib Hydrochloride, Bevacizumab)
Arm/Group Description:	Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.	Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
Overall Number of Participants Analyzed	45	43
Measure Type: Count of Participants; Unit of Measure: Participants
	13 28.9%	31 72.1%

6. Other Pre-specified Outcome

Title	EGFR Mutations Detected in Plasma Deoxyribonucleic Acid (DNA)
Description	Agreement of EGFR mutations detected in plasma DNA with those detected in tumor DNA will be evaluated.
Time Frame	Up to 6 years

Outcome Measure Data Not Reported

7. Other Pre-specified Outcome

Title	EGFR Mutations Detected in Tumor Deoxyribonucleic Acid (DNA)
Description	Agreement of EGFR mutations detected in plasma DNA with those detected in tumor DNA will be evaluated.
Time Frame	Up to 6 years

Outcome Measure Data Not Reported

8. Other Pre-specified Outcome

Title	Prevalence of EGFR T790M Resistance Mutations From Pretreatment > Tumor Biopsies Using More Sensitive Mutation Detection Methods
Description	Tested using Cox proportional hazard model after adjusting for treatment effect. The robustness of treatment effect in different subgroups will be examined in a Forest plot.
Time Frame	Baseline

Outcome Measure Data Not Reported

9. Other Pre-specified Outcome

Title	EGFR T790M Mutations
Description	Detected from pre-treatment tumor specimen using allele specific quantitative polymerase chain reaction (PCR). The PFS of patients with EGFR T790M mutations will be estimated and the survival difference will be tested using Cox proportional hazard model after adjusting for treatment effect. The robustness of treatment effect in different subgroups will be examined in a Forest plot.
Time Frame	Up to 6 years

Outcome Measure Data Not Reported

10. Other Pre-specified Outcome

Title	Predictive Value of Plasma VEGF-A Levels on Progression Free Survival in Patients Treated With Erlotinib Hydrochloride Alone or in Combination With Bevacizumab
Description	Evaluated using time-dependent receiver operating characteristic curve and area under curve.
Time Frame	Baseline

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Up to 42 days after treatment discontinuation
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Arm A (Erlotinib Hydrochloride)		Arm B (Erlotinib Hydrochloride, Bevacizumab)
Arm/Group Description	Patients receive 150 mg erlotinib hydrochloride PO QD on days 1-21.		Patients receive 150 mg erlotinib hydrochloride as in Arm A and 15 mg/kg bevacizumab IV over 30-90 minutes on day 1.
All-Cause Mortality
	Arm A (Erlotinib Hydrochloride)		Arm B (Erlotinib Hydrochloride, Bevacizumab)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	23/45 (51.11%)		27/43 (62.79%)
Serious Adverse Events
	Arm A (Erlotinib Hydrochloride)		Arm B (Erlotinib Hydrochloride, Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/45 (26.67%)		17/43 (39.53%)
Cardiac disorders
Acute coronary syndrome † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Chest pain - cardiac † 1	1/45 (2.22%)	1	1/43 (2.33%)	1
Gastrointestinal disorders
Abdominal pain † 1	1/45 (2.22%)	1	1/43 (2.33%)	1
Anal hemorrhage † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Diarrhea † 1	2/45 (4.44%)	2	1/43 (2.33%)	1
General disorders
Sudden death NOS † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Infections and infestations
Kidney infection † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Lung infection † 1	2/45 (4.44%)	3	0/43 (0.00%)	0
Nail infection † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Rash pustular † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Injury, poisoning and procedural complications
Fall † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Investigations
Alanine aminotransferase increased † 1	1/45 (2.22%)	2	0/43 (0.00%)	0
Aspartate aminotransferase increased † 1	1/45 (2.22%)	2	0/43 (0.00%)	0
Blood bilirubin increased † 1	1/45 (2.22%)	1	1/43 (2.33%)	1
Cardiac troponin I increased † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Metabolism and nutrition disorders
Dehydration † 1	0/45 (0.00%)	0	2/43 (4.65%)	2
Hyponatremia † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Nervous system disorders
Cognitive disturbance † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Dizziness † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Syncope † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Psychiatric disorders
Confusion † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Renal and urinary disorders
Proteinuria † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Urinary retention † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage † 1	0/45 (0.00%)	0	1/43 (2.33%)	2
Dyspnea † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Pleural effusion † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Skin and subcutaneous tissue disorders
Erythema multiforme † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Pain of skin † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Rash acneiform † 1	1/45 (2.22%)	1	3/43 (6.98%)	3
Vascular disorders
Hypertension † 1	4/45 (8.89%)	4	2/43 (4.65%)	3
Thromboembolic event † 1	2/45 (4.44%)	2	1/43 (2.33%)	2
1 Term from vocabulary, MedDRA 12; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm A (Erlotinib Hydrochloride)		Arm B (Erlotinib Hydrochloride, Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/45 (95.56%)		43/43 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	2/45 (4.44%)	5	0/43 (0.00%)	0
Blood and lymph sys disorders - Oth Spec † 1	2/45 (4.44%)	3	1/43 (2.33%)	1
Leukocytosis † 1	1/45 (2.22%)	1	2/43 (4.65%)	5
Cardiac disorders
Acute coronary syndrome † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Cardiac disorders - Other, specify † 1	1/45 (2.22%)	4	0/43 (0.00%)	0
Left ventricular systolic dysfunction † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Ear and labyrinth disorders
Ear and labyrinth disorders - Oth spec † 1	0/45 (0.00%)	0	2/43 (4.65%)	2
Hearing impaired † 1	0/45 (0.00%)	0	1/43 (2.33%)	29
Tinnitus † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Vertigo † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Eye disorders
Cataract † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Dry eye † 1	1/45 (2.22%)	1	1/43 (2.33%)	1
Eye disorders - Other, specify † 1	2/45 (4.44%)	3	2/43 (4.65%)	5
Periorbital edema † 1	1/45 (2.22%)	1	1/43 (2.33%)	2
Watering eyes † 1	1/45 (2.22%)	7	0/43 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/45 (0.00%)	0	4/43 (9.30%)	5
Anal hemorrhage † 1	3/45 (6.67%)	16	3/43 (6.98%)	24
Ascites † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Cheilitis † 1	1/45 (2.22%)	3	0/43 (0.00%)	0
Colitis † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Diarrhea † 1	37/45 (82.22%)	606	38/43 (88.37%)	528
Dyspepsia † 1	1/45 (2.22%)	4	1/43 (2.33%)	3
Gastroesophageal reflux disease † 1	0/45 (0.00%)	0	2/43 (4.65%)	45
Gastrointestinal disorders - Oth spec † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Gastrointestinal pain † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Mucositis oral † 1	2/45 (4.44%)	2	3/43 (6.98%)	4
Nausea † 1	3/45 (6.67%)	10	5/43 (11.63%)	9
Oral hemorrhage † 1	2/45 (4.44%)	28	5/43 (11.63%)	9
Rectal hemorrhage † 1	2/45 (4.44%)	2	2/43 (4.65%)	28
Stomach pain † 1	0/45 (0.00%)	0	1/43 (2.33%)	5
Vomiting † 1	2/45 (4.44%)	2	1/43 (2.33%)	1
General disorders
Edema limbs † 1	1/45 (2.22%)	1	1/43 (2.33%)	2
Fatigue † 1	10/45 (22.22%)	44	14/43 (32.56%)	39
Fever † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Gen disord and admin site conds-Oth spec † 1	1/45 (2.22%)	11	0/43 (0.00%)	0
Malaise † 1	0/45 (0.00%)	0	2/43 (4.65%)	5
Pain † 1	2/45 (4.44%)	3	1/43 (2.33%)	1
Hepatobiliary disorders
Hepatic hemorrhage † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Immune system disorders
Allergic reaction † 1	2/45 (4.44%)	2	0/43 (0.00%)	0
Infections and infestations
Anorectal infection † 1	0/45 (0.00%)	0	1/43 (2.33%)	2
Bronchial infection † 1	0/45 (0.00%)	0	1/43 (2.33%)	3
Conjunctivitis † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Gum infection † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Infections and infestations - Oth spec † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Lip infection † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Lung infection † 1	0/45 (0.00%)	0	3/43 (6.98%)	3
Nail infection † 1	2/45 (4.44%)	5	1/43 (2.33%)	23
Papulopustular rash † 1	0/45 (0.00%)	0	1/43 (2.33%)	5
Paronychia † 1	6/45 (13.33%)	37	3/43 (6.98%)	10
Sinusitis † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Skin infection † 1	2/45 (4.44%)	3	1/43 (2.33%)	2
Urinary tract infection † 1	3/45 (6.67%)	4	3/43 (6.98%)	3
Injury, poisoning and procedural complications
Bruising † 1	0/45 (0.00%)	0	1/43 (2.33%)	3
Investigations
Activated partial throm time prolonged † 1	1/45 (2.22%)	9	0/43 (0.00%)	0
Alanine aminotransferase increased † 1	2/45 (4.44%)	4	2/43 (4.65%)	2
Alkaline phosphatase increased † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Aspartate aminotransferase increased † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Blood bilirubin increased † 1	8/45 (17.78%)	19	1/43 (2.33%)	4
Cardiac troponin I increased † 1	1/45 (2.22%)	21	0/43 (0.00%)	0
Creatinine increased † 1	2/45 (4.44%)	2	2/43 (4.65%)	6
Lymphocyte count decreased † 1	5/45 (11.11%)	33	1/43 (2.33%)	1
Lymphocyte count increased † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Weight gain † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Weight loss † 1	4/45 (8.89%)	19	6/43 (13.95%)	33
Metabolism and nutrition disorders
Anorexia † 1	4/45 (8.89%)	24	7/43 (16.28%)	14
Dehydration † 1	3/45 (6.67%)	4	1/43 (2.33%)	1
Glucose intolerance † 1	0/45 (0.00%)	0	1/43 (2.33%)	20
Hyperglycemia † 1	0/45 (0.00%)	0	2/43 (4.65%)	11
Hyperkalemia † 1	0/45 (0.00%)	0	1/43 (2.33%)	2
Hypocalcemia † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Hypokalemia † 1	1/45 (2.22%)	2	1/43 (2.33%)	1
Hyponatremia † 1	1/45 (2.22%)	1	3/43 (6.98%)	10
Hypophosphatemia † 1	2/45 (4.44%)	4	2/43 (4.65%)	13
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/45 (2.22%)	2	0/43 (0.00%)	0
Back pain † 1	2/45 (4.44%)	3	0/43 (0.00%)	0
Buttock pain † 1	1/45 (2.22%)	2	0/43 (0.00%)	0
Flank pain † 1	1/45 (2.22%)	2	0/43 (0.00%)	0
Generalized muscle weakness † 1	0/45 (0.00%)	0	2/43 (4.65%)	3
Musculoskeletal, conn tissue - Oth spec † 1	1/45 (2.22%)	3	1/43 (2.33%)	1
Myalgia † 1	1/45 (2.22%)	8	1/43 (2.33%)	1
Pain in extremity † 1	2/45 (4.44%)	2	1/43 (2.33%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec † 1	1/45 (2.22%)	2	0/43 (0.00%)	0
Nervous system disorders
Cerebrospinal fluid leakage † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Concentration impairment † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Dizziness † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Dysgeusia † 1	2/45 (4.44%)	7	3/43 (6.98%)	23
Encephalopathy † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Headache † 1	3/45 (6.67%)	3	1/43 (2.33%)	1
Memory impairment † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Nervous system disorders - Oth spec † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Neuralgia † 1	0/45 (0.00%)	0	1/43 (2.33%)	2
Peripheral motor neuropathy † 1	1/45 (2.22%)	3	0/43 (0.00%)	0
Peripheral sensory neuropathy † 1	0/45 (0.00%)	0	2/43 (4.65%)	3
Presyncope † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Syncope † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Transient ischemic attacks † 1	0/45 (0.00%)	0	2/43 (4.65%)	2
Psychiatric disorders
Anxiety † 1	0/45 (0.00%)	0	2/43 (4.65%)	2
Confusion † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Delirium † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Depression † 1	1/45 (2.22%)	1	1/43 (2.33%)	6
Insomnia † 1	4/45 (8.89%)	19	0/43 (0.00%)	0
Renal and urinary disorders
Chronic kidney disease † 1	1/45 (2.22%)	1	1/43 (2.33%)	4
Hematuria † 1	15/45 (33.33%)	102	12/43 (27.91%)	79
Proteinuria † 1	15/45 (33.33%)	106	24/43 (55.81%)	218
Reproductive system and breast disorders
Vaginal hemorrhage † 1	0/45 (0.00%)	0	1/43 (2.33%)	4
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage † 1	3/45 (6.67%)	3	1/43 (2.33%)	12
Cough † 1	2/45 (4.44%)	3	0/43 (0.00%)	0
Dyspnea † 1	2/45 (4.44%)	8	5/43 (11.63%)	6
Epistaxis † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Nasal congestion † 1	0/45 (0.00%)	0	2/43 (4.65%)	2
Pleural effusion † 1	1/45 (2.22%)	1	2/43 (4.65%)	2
Pneumonitis † 1	0/45 (0.00%)	0	1/43 (2.33%)	6
Pulmonary edema † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Resp, thoracic, mediastinal - Oth spec † 1	0/45 (0.00%)	0	3/43 (6.98%)	34
Skin and subcutaneous tissue disorders
Alopecia † 1	4/45 (8.89%)	11	3/43 (6.98%)	54
Bullous dermatitis † 1	0/45 (0.00%)	0	1/43 (2.33%)	5
Dry skin † 1	6/45 (13.33%)	34	6/43 (13.95%)	74
Erythema multiforme † 1	1/45 (2.22%)	3	0/43 (0.00%)	0
Nail loss † 1	1/45 (2.22%)	2	0/43 (0.00%)	0
Pain of skin † 1	0/45 (0.00%)	0	2/43 (4.65%)	3
Palmar-plantar erythrodysesthesia syndrm † 1	0/45 (0.00%)	0	1/43 (2.33%)	1
Photosensitivity † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Pruritus † 1	0/45 (0.00%)	0	2/43 (4.65%)	17
Rash acneiform † 1	40/45 (88.89%)	586	42/43 (97.67%)	732
Rash maculo-papular † 1	3/45 (6.67%)	7	3/43 (6.98%)	11
Skin and subcut tissue disord - Oth spec † 1	2/45 (4.44%)	2	2/43 (4.65%)	2
Surgical and medical procedures
Surgical and medical proced - Oth spec † 1	0/45 (0.00%)	0	2/43 (4.65%)	2
Vascular disorders
Hypertension † 1	23/45 (51.11%)	413	36/43 (83.72%)	617
Hypotension † 1	1/45 (2.22%)	2	0/43 (0.00%)	0
Phlebitis † 1	1/45 (2.22%)	1	0/43 (0.00%)	0
Thromboembolic event † 1	1/45 (2.22%)	1	2/43 (4.65%)	42
1 Term from vocabulary, MedDRA 12; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Thomas E. Stinchcombe, M.D.
• Organization: Duke University
• Phone: 507/284-4565
• EMail: thomas.stinchcombe@duke.edu

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

Stinchcombe TE, Janne PA, Wang X, Bertino EM, Weiss J, Bazhenova L, Gu L, Lau C, Paweletz C, Jaslowski A, Gerstner GJ, Baggstrom MQ, Graziano S, Bearden J 3rd, Vokes EE. Effect of Erlotinib Plus Bevacizumab vs Erlotinib Alone on Progression-Free Survival in Patients With Advanced EGFR-Mutant Non-Small Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Oct 1;5(10):1448-1455. doi: 10.1001/jamaoncol.2019.1847.

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT01532089
• Other Study ID Numbers: RC1126; NCI-2012-00053 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 11-006881; RC1126 ( Other Identifier: Academic and Community Cancer Research United ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Submitted: February 7, 2012
• First Posted: February 14, 2012
• Results First Submitted: December 9, 2019
• Results First Posted: December 26, 2019
• Last Update Posted: October 6, 2020