A Study of Erlotinib (Tarceva) After Surgery With or Without Adjuvant Chemotherapy in Non-Small Cell Lung Carcinoma (NSCLC) Patients Who Have Epidermal Growth Factor Receptor (EGFR) Positive Tumors (RADIANT)

• ClinicalTrials.gov Identifier: NCT00373425
• Recruitment Status: Completed
• First Posted: September 8, 2006
• Results First Posted: June 3, 2014
• Last Update Posted: September 17, 2015
• Sponsor: OSI Pharmaceuticals
• Information provided by (Responsible Party): Astellas Pharma Inc ( OSI Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer
• Interventions: Drug: Erlotinib; Drug: Placebo
• Enrollment: 1252

Participant Flow

Recruitment Details	Patients with stage IB to IIIA epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) were enrolled globally. 1252 patients were enrolled however 2 patients did not have adequate Health Insurance Portability and Accountability Act (HIPAA) documentation and were removed from the database.
Pre-assignment Details	Participants randomized prior to 7 November 2007 comprise the Breached-Protocol Cohort (BPC); those who had not discontinued were offered open-label erlotinib for up to 2 years. Participants randomized subsequently are referred to as the Randomized Cohort.

Arm/Group Title	RC: Erlotinib	RC: Placebo	BPC-NOLC: Erlotinib/Placebo	BPC-NOLC: Placebo Only	BPC-OLC: Erlotinib
Arm/Group Description	Participants in the randomized cohort (RC) who received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants in the randomized cohort (RC) who received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and received at least one dose of erlotinib.	The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and did not receive any erlotinib.	The BPC open-label cohort (BPC-OLC) includes participants randomized prior to 07 November 2007 who received at least 1 dose of study drug after being randomized, who entered the open-label erlotinib period. Data presented for the BPC-OLC included data from both the blinded period and the open-label erlotinib period.
Period Title: Overall Study
Started	623	350	134	11	132
Received Treatment	612	342	134	7	132
Completed	253 [1]	197 [1]	0 [1]	0 [1]	60 [1]
Not Completed	370	153	134	11	72
Reason Not Completed
Relapse of NSCLC	116	104	19	2	26
Adverse Event	191	22	59	0	34
Patient request	35	18	43	6	7
Medical/ethical/noncompliance reason	21	9	10	2	5
Death	7	0	3	1	0
[1] Completed 2 years of study treatment

Baseline Characteristics

Arm/Group Title		RC: Erlotinib	RC: Placebo	BPC-NOLC: Erlotinib/Placebo	BPC-NOLC: Placebo Only	BPC-OLC: Erlotinib	Total
Arm/Group Description		Participants in the randomized cohort (RC) who received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants in the randomized cohort (RC) who received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and received at least one dose of erlotinib.	The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and did not receive any erlotinib.	The BPC open-label cohort (BPC-OLC) includes participants randomized prior to 07 November 2007 who received at least 1 dose of study drug after being randomized, who entered the open-label erlotinib period. Data presented for the BPC-OLC included data from both the blinded period and the open-label erlotinib period.	Total of all reporting groups
Overall Number of Baseline Participants		623	350	134	11	132	1250
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
Randomized Cohort		62.0 (9.28)	61.8 (9.34)	NA [1] (NA)	NA [1] (NA)	NA [1] (NA)	61.9 (9.30)
Breached Protocol Cohort, No Open label		NA [2] (NA)	NA [2] (NA)	64.4 (9.33)	62.7 (6.23)	NA [2] (NA)	64.3 (9.13)
Breached Protocol Cohort, Open label		NA [3] (NA)	NA [3] (NA)	NA [3] (NA)	NA [3] (NA)	61.8 (9.35)	61.8 (9.35)
		[1] Randomized Cohort only; [2] Breached Protocol Cohort - No Open Label only; [3] Breached Protocol Cohort - Open Label only
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
	Female	257 41.3%	141 40.3%	47 35.1%	2 18.2%	57 43.2%	504 40.3%
	Male	366 58.7%	209 59.7%	87 64.9%	9 81.8%	75 56.8%	746 59.7%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
White		500	279	114	10	111	1014
Black		14	11	4	0	4	33
Asian		107	60	15	1	17	200
American Indian/Alaska Native		1	0	1	0	0	2
Other		1	0	0	0	0	1
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
Not Hispanic or Latino		583	322	123	11	124	1163
Hispanic or Latino		40	28	11	0	8	87
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
Grade 0		385	211	75	5	77	753
Grade 1		230	134	55	6	54	479
Grade 2		6	5	3	0	1	15
Not measured		2	0	1	0	0	3
		[1] Measure Description: ECOG criteria: 0: Fully active. 1: Ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of all selfcare. 3: Capable of limited selfcare, confined to bed or chair more than 50% of waking hours. 4: Completely disabled, no selfcare, totally confined to bed or chair. 5: Dead.
Cigarette Smoking History; Measure Type: Number; Unit of measure: Participants	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
Never smoked or ≤ 100 cigarettes in lifetime		129	70	19	1	19	238
Former smoker		423	240	103	9	104	879
Current smoker		71	40	12	1	9	133
Histology; Measure Type: Number; Unit of measure: Participants	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
Adenocarcinoma		367	211	73	3	76	730
Squamous cell carcinoma		196	111	48	8	49	412
Undifferentiated large cell		22	8	6	0	4	40
Mixed NSCLC		29	18	5	0	1	53
Other		9	2	2	0	2	15
Extent of Disease at Diagnosis [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
Stage IA		1	2	1	0	0	4
Stage IB		329	167	64	4	80	644
Stage IIA		42	24	10	1	9	86
Stage IIB		155	99	36	4	23	317
Stage IIIA		93	58	21	1	17	190
Stage IIIB		2	0	2	0	3	7
Stage IV		1	0	0	1	0	2
		[1] Measure Description: Staging is based on the size of the main tumor and whether it has grown into nearby areas, the spread of cancer to nearby lymph nodes and whether the cancer has spread (metastasized) to other organs of the body.
Adjuvant Chemotherapy; Measure Type: Number; Unit of measure: Participants	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
Yes		315	200	63	5	68	651
No		308	150	71	6	64	599
Epidermal Growth Factor Receptor (EGFR) Mutation Status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
Activating mutation-positive		102	59	10	0	16	187
Wild-type		458	245	116	11	107	937
Undetermined		29	16	1	0	1	47
Activating mutation not positive		30	27	5	0	6	68
Not Available		4	3	2	0	2	11
		[1] Measure Description: EGFR mutation status: Activating mutation-positive: exon 19 deletion or exon 21 L858R (or both) detected. Wild-type: neither exon 19 deletion nor exon 21 L858R or any other mutation (exon 18, 19, 20 and 21) detected or undetermined. Undetermined: exon 19 deletion or exon 21 L858R (or both) mutation status undetermined. Activating mutation not positive: neither exon 19 deletion nor exon 21 L858R detected or undetermined (includes other mutation positive and other mutation status undetermined).
EGFR Gene Amplification [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	623 participants	350 participants	134 participants	11 participants	132 participants	1250 participants
Positive		445	255	84	8	100	892
Negative		167	87	49	3	32	338
Undetermined		11	8	1	0	0	20
		[1] Measure Description: Analysis of tumor tissue by fluorescent in situ hybridization (FISH), positivity was defined as amplification (EGFR gene to chromosome ratio of ≥ 2 or ≥ 15 EGFR gene copies in ≥ 10% of tumor cells) or high polysomy (≥ 4 EGFR gene copies in ≥ 40% of tumor cells) .

Outcome Measures

1. Primary Outcome

Title	Disease Free Survival (DFS)
Description	DFS is the time from the date of randomization until the first day non-small cell lung cancer (NSCLC) relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date.
Time Frame	Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months).

Outcome Measure Data

Analysis Population Description

Randomized cohort full analysis set (all randomized participants).

Arm/Group Title	Erlotinib	Placebo
Arm/Group Description:	Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed	623	350
Median (95% Confidence Interval); Unit of Measure: months
	50.5 [1]; (44.7 to NA)	48.2 [1]; (36.0 to NA)

[1]

Not estimable due to the low number of events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erlotinib, Placebo
	Comments	The null hypothesis that DFS distributions of the 2 arms were equivalent was tested using an unstratified 2-sided log-rank test at the 0.05 level. The primary analysis of DFS was performed when at least 410 events had accrued. If the result of the primary analysis of DFS was statistically significant favoring the erlotinib treatment arm, the null hypothesis of no treatment difference of key secondary efficacy variables was tested under a hierarchical testing procedure.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3235
	Comments	If the primary analysis of DFS was not statistically significant, the hierarchical testing procedure would stop and all key secondary efficacy analyses would be nonsignificant; any further analysis of these outcomes would be considered exploratory.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.741 to 1.104
	Estimation Comments	Hazard ratio: erlotinib to placebo

2. Primary Outcome

Title	Disease Free Survival (DFS)
Description	DFS is the time from the date of randomization until the first day that non-small cell lung cancer (NSCLC) relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date.
Time Frame	Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cutoff date of 11 June 2014 (maximum time on follow-up was 78 months).

Outcome Measure Data

Analysis Population Description

Randomized cohort full analysis set (all randomized participants).

Arm/Group Title	Erlotinib	Placebo
Arm/Group Description:	Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed	623	350
Median (95% Confidence Interval); Unit of Measure: months
	55.0; (47.0 to 64.5)	56.2; (39.7 to 65.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erlotinib, Placebo
	Comments	The null hypothesis that DFS distributions of the 2 arms were equivalent was tested using an unstratified 2-sided log-rank test at the 0.05 level.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5620
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.780 to 1.144
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive.
Time Frame	Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months).

Outcome Measure Data

Analysis Population Description

Randomized cohort full analysis set

Arm/Group Title	Erlotinib	Placebo
Arm/Group Description:	Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed	623	350
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Could not be estimated due to the low number of events

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive.
Time Frame	Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months).

Outcome Measure Data

Analysis Population Description

Randomized cohort full analysis set

Arm/Group Title	Erlotinib	Placebo
Arm/Group Description:	Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed	623	350
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (77.9 to NA)	NA [1]; (NA to NA)

[1]

Could not be estimated due to the low number of events

5. Secondary Outcome

Title	Disease-free Survival in Participants With EGFR Mutation - Positive Tumors
Description	Disease-free survival (DFS) is the time from the date of randomization until the first day NSCLC relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.
Time Frame	Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months).

Outcome Measure Data

Analysis Population Description

Randomized cohort full analysis set participants who are EGFR mutation positive

Arm/Group Title	Erlotinib	Placebo
Arm/Group Description:	Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed	102	59
Median (95% Confidence Interval); Unit of Measure: months
	46.4 [1]; (39.8 to NA)	28.5 [1]; (16.7 to NA)

[1]

Could not be estimated due to low number of events

6. Secondary Outcome

Title	Disease-free Survival in Participants With EGFR Mutation - Positive Tumors
Description	Disease-free survival (DFS) is the time from the date of randomization until the first day NSCLC relapse is documented by radiological exam and/or biopsy, or until death in the absence of relapse. After randomization, NSCLC relapse was based on radiological evidence or biopsy, as determined by the investigator. Participants without a DFS event were censored on the last adequate radiological assessment date. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.
Time Frame	Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months).

Outcome Measure Data

Analysis Population Description

Randomized cohort full analysis set participants who are EGFR mutation positive

Arm/Group Title	Erlotinib	Placebo
Arm/Group Description:	Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed	102	59
Median (95% Confidence Interval); Unit of Measure: months
	47.8; (39.8 to 60.8)	28.5; (16.7 to 61.4)

7. Secondary Outcome

Title	Overall Survival in Participants With EGFR Mutation - Positive Tumors
Description	Overall survival is defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.
Time Frame	Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 08 April 2013 (maximum time on follow-up was 64 months)

Outcome Measure Data

Analysis Population Description

Randomized cohort full analysis participants who were EGFR mutation positive

Arm/Group Title	Erlotinib	Placebo
Arm/Group Description:	Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed	102	59
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (55.4 to NA)

[1]

Could not be estimated due to low number of events

8. Secondary Outcome

Title	Overall Survival in Participants With EGFR Mutation - Positive Tumors
Description	Overall survival is defined as the time from the date of randomization until the documented date of death. Participants who were still alive were censored on the last day they were known to be alive. Activating EGFR mutation-positive is defined as exon 19 deletion or exon 21 L858R (or both) detected.
Time Frame	Every 3 months during active phase and every 6 months during long term follow-up up to 5 years and yearly thereafter until the data cut-off date of 11 June 2014 (maximum time on follow-up was 78 months)

Outcome Measure Data

Analysis Population Description

Randomized cohort full analysis participants who were EGFR mutation positive

Arm/Group Title	Erlotinib	Placebo
Arm/Group Description:	Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed	102	59
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Could not be estimated due to the low number of events

9. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An AE was defined as any untoward medical occurrence in a study participant and did not necessarily have a causal relationship with study treatment. An AE was considered serious if it resulted in death, a life-threatening situation, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a participant, other important medical events, or is on the Astellas Always Serious List. A drug-related AE was any AE with at least a possible relationship to study treatment as assessed by the investigator. Severity was graded by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v3.0, where Grade 1=Mild AE; Grade=2 Moderate AE; Grade 3=Severe AE; Grade 4=Life-threatening or disabling; Grade 5=Death related to AE. AEs leading to death include deaths that occurred more than 30 days after the last dose of study drug.
Time Frame	From the date of first dose of study drug until 30 days after the last dose. The median time on treatment was 11.9 months for erlotinib and 21.9 months for placebo. Data are based off the 11 June 2014 data cut-off date.

Outcome Measure Data

Analysis Population Description

Randomized Cohort, safety analysis set: all randomized participants who received at least one dose of study drug. One participant in the Randomized Cohort assigned to the erlotinib arm received placebo instead due to a dispensing error and is included in the placebo group for safety analyses.

Arm/Group Title	Erlotinib	Placebo
Arm/Group Description:	Participants received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.
Overall Number of Participants Analyzed	611	343
Measure Type: Number; Unit of Measure: participants
Any adverse event (AE)	599	307
Grade 3 or higher adverse event	279	96
Serious adverse event (SAE)	118	79
AE leading to discontinuation of study drug	205	29
AE leading to death	14	5
AE leading to dose reduction	150	9
AE leading to dose interruption	114	23
AE leading to dose interruption and reduction	156	5
Drug-related AE	572	181
Drug-related serious AE	15	5
Drug-related AE leading to discontinuation	163	8

Adverse Events

Time Frame	From the first dose of study drug until 30 days after the last dose. Maximum time on treatment for the Randomized Cohort was 24 months; maximum time on treatment for the BPC was 13 months on blinded study drug and 26 months on open-label erlotinib.
Adverse Event Reporting Description	One participant in the Randomized Cohort assigned to the erlotinib arm received placebo instead due to a dispensing error and is included in the placebo group for safety analyses. For the Breached Protocol Cohort safety analyses are based on the total no open-label and open-label populations. Safety data are based on the 11 June 2014 cut-off date.
Arm/Group Title	RC: Erlotinib	RC: Placebo	BPC-NOLC: Erlotinib/Placebo	BPC-NOLC: Placebo Only	BPC-OLC: Erlotinib
Arm/Group Description	Participants in the randomized cohort (RC) who received 150 mg/day erlotinib orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	Participants in the randomized cohort (RC) who received matching placebo tablets orally for 2 years or until relapse, death, participant request or investigator decision to discontinue study drug, or intolerable toxicity.	The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and received at least one dose of erlotinib.	The BPC no open-label cohort (BPC-NOLC) includes participants randomized prior to 07 November 2007 who did not participate in the open-label erlotinib period and who were previously randomized to receive either erlotinib or placebo in the blinded period, and did not receive any erlotinib.	The BPC open-label cohort (BPC-OLC) includes participants randomized prior to 07 November 2007 who received at least 1 dose of study drug after being randomized, who entered the open-label erlotinib period. Data presented for the BPC-OLC included data from both the blinded period and the open-label erlotinib period.
All-Cause Mortality
	RC: Erlotinib	RC: Placebo	BPC-NOLC: Erlotinib/Placebo	BPC-NOLC: Placebo Only	BPC-OLC: Erlotinib
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events
	RC: Erlotinib	RC: Placebo	BPC-NOLC: Erlotinib/Placebo	BPC-NOLC: Placebo Only	BPC-OLC: Erlotinib
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	118/611 (19.31%)	79/343 (23.03%)	21/134 (15.67%)	1/11 (9.09%)	41/132 (31.06%)
Blood and lymphatic system disorders
Anaemia † 1	4/611 (0.65%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Lymphadenopathy † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Haemolytic anaemia † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cardiac disorders
Myocardial infarction † 1	3/611 (0.49%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pericarditis † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Acute myocardial infarction † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Atrial fibrillation † 1	1/611 (0.16%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	1/132 (0.76%)
Cardiac failure † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cardio-respiratory arrest † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pericardial effusion † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Acute coronary syndrome † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Angina pectoris † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Angina unstable † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Arrhythmia † 1	0/611 (0.00%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	1/132 (0.76%)
Ischaemic cardiomyopathy † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Coronary artery disease † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	1/132 (0.76%)
Cardiac failure congestive † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Congenital, familial and genetic disorders
Rathke's cleft cyst † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Atrial septal defect † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Ear and labyrinth disorders
Deafness † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Deafness neurosensory † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Endocrine disorders
Thyroid cyst † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Eye disorders
Cataract † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Blindness † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Retinal haemorrhage † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Gastrointestinal disorders
Diarrhoea † 1	4/611 (0.65%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	1/132 (0.76%)
Duodenal ulcer † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Gastrointestinal haemorrhage † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Abdominal pain † 1	1/611 (0.16%)	3/343 (0.87%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Dysphagia † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Gastric ulcer † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Gingival bleeding † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Haematemesis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Ileus † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Intestinal obstruction † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Oesophagitis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Small intestinal obstruction † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Subileus † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Volvulus † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Colitis ischaemic † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Enterovesical fistula † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Gastrooesophageal reflux disease † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Nausea † 1	0/611 (0.00%)	1/343 (0.29%)	2/134 (1.49%)	0/11 (0.00%)	1/132 (0.76%)
Pancreatitis † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Rectal haemorrhage † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Vomiting † 1	0/611 (0.00%)	1/343 (0.29%)	2/134 (1.49%)	0/11 (0.00%)	1/132 (0.76%)
Diarrhoea haemorrhagic † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Peptic ulcer perforation † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Peritonitis † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Enteritis † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Gastric dysplasia † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Haemorrhoids † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Tooth resorption † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Upper gastrointestinal haemorrhage † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
General disorders
Asthenia † 1	3/611 (0.49%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Fatigue † 1	2/611 (0.33%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Chest pain † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Death † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
General physical health deterioration † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Multi-organ failure † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pyrexia † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Pain † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Performance status decreased † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Sudden death † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Hepatobiliary disorders
Cholecystitis acute † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cholangitis acute † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cholecystitis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Jaundice † 1	0/611 (0.00%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Immune system disorders
Anaphylactic shock † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Infections and infestations
Pneumonia † 1	8/611 (1.31%)	2/343 (0.58%)	2/134 (1.49%)	0/11 (0.00%)	3/132 (2.27%)
Respiratory tract infection † 1	4/611 (0.65%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Bronchitis † 1	2/611 (0.33%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Sepsis † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Urinary tract infection † 1	2/611 (0.33%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Appendicitis † 1	1/611 (0.16%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Bronchopneumonia † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cellulitis † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Clostridial infection † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Dermatitis infected † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Diverticulitis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Eczema infected † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Empyema † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Haematoma infection † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Osteomyelitis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pertussis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pyelonephritis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Upper respiratory tract infection † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Bronchitis acute † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Clostridium difficile colitis † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Herpes zoster † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Lobar pneumonia † 1	0/611 (0.00%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Lung infection † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Meningitis viral † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pulmonary tuberculosis † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Wound infection staphylococcal † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Device related infection † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Arthritis infective † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Bacterial infection † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Nasal abscess † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Nasopharyngitis † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Pneumonia bacterial † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Injury, poisoning and procedural complications
Fall † 1	3/611 (0.49%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Clavicle fracture † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Haemothorax † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Injury † 1	1/611 (0.16%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Laceration † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Polytraumatism † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Post procedural haematoma † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Procedural pain † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Rib fracture † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Spinal compression fracture † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Ankle fracture † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Bronchial anastomosis complication † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Concussion † 1	0/611 (0.00%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Femur fracture † 1	0/611 (0.00%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Road traffic accident † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pelvic fracture † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	1/132 (0.76%)
Suture rupture † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Hip fracture † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Incisional hernia † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Postoperative fever † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Investigations
Blood bilirubin increased † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Weight decreased † 1	0/611 (0.00%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Blood creatinine increased † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	3/611 (0.49%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Anorexia † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Fluid retention † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Hypokalaemia † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Hyponatraemia † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Oral intake reduced † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Hypercalcaemia † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Back pain † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Bone pain † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Flank pain † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Muscular weakness † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pain in extremity † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Spinal column stenosis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Arthralgia † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Muscle haemorrhage † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Musculoskeletal chest pain † 1	0/611 (0.00%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Musculoskeletal pain † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Rotator cuff syndrome † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Osteoarthritis † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Spondylolisthesis † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression † 1	4/611 (0.65%)	3/343 (0.87%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Laryngeal cancer † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Lung squamous cell carcinoma stage unspecified † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Metastases to central nervous system † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Neurilemmoma † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Prostate cancer † 1	3/611 (0.49%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	3/132 (2.27%)
Throat cancer † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cancer pain † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Chronic myeloid leukaemia † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Colon cancer † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Renal cell carcinoma stage unspecified † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Sarcoma † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Colon adenoma † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Lung neoplasm † 1	5/611 (0.82%)	3/343 (0.87%)	0/134 (0.00%)	0/11 (0.00%)	2/132 (1.52%)
Small cell lung cancer stage unspecified † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	2/132 (1.52%)
Basal cell carcinoma † 1	1/611 (0.16%)	5/343 (1.46%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Bladder cancer † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Conjunctival neoplasm † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Malignant ascites † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Malignant melanoma † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Prostate cancer stage I † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Squamous cell carcinoma † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Squamous cell carcinoma of skin † 1	0/611 (0.00%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Thyroid cancer † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Thyroid neoplasm † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Tonsil cancer † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Uterine cancer † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Nervous system disorders
Cerebrovascular accident † 1	3/611 (0.49%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Hemiparesis † 1	3/611 (0.49%)	4/343 (1.17%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Headache † 1	2/611 (0.33%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	1/132 (0.76%)
Loss of consciousness † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cerebral infarction † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cerebral ischaemia † 1	1/611 (0.16%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Intracranial pressure increased † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Memory impairment † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Monoparesis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Neuropathy peripheral † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Peripheral motor neuropathy † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Presyncope † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Convulsion † 1	1/611 (0.16%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Dysphasia † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
IIIrd nerve paralysis † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Peripheral sensory neuropathy † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Syncope † 1	0/611 (0.00%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Transient ischaemic attack † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cerebral artery embolism † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Facial paresis † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Normal pressure hydrocephalus † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Sudden onset of sleep † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Balance disorder † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Brain mass † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Dizziness † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Ischaemic stroke † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Neuralgia † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Cerebellar infarction † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Epilepsy † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Psychiatric disorders
Confusional state † 1	1/611 (0.16%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Disorientation † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Mental status changes † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	2/132 (1.52%)
Inappropriate affect † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Renal and urinary disorders
Renal failure acute † 1	4/611 (0.65%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Nephrolithiasis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Urinary bladder haemorrhage † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Urinary incontinence † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Calculus ureteric † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Urethral obstruction † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Reproductive system and breast disorders
Uterovaginal prolapse † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	6/611 (0.98%)	5/343 (1.46%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Pulmonary embolism † 1	3/611 (0.49%)	5/343 (1.46%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pleural effusion † 1	2/611 (0.33%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Asthma † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Bronchial hyperreactivity † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Cough † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Epistaxis † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Hypoxia † 1	1/611 (0.16%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Lung disorder † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pneumonia aspiration † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pulmonary congestion † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Respiratory failure † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Chronic obstructive pulmonary disease † 1	0/611 (0.00%)	3/343 (0.87%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Lower respiratory tract inflammation † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Pneumothorax † 1	0/611 (0.00%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Pulmonary infarction † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Acute respiratory distress syndrome † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Apnoea † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	1/11 (9.09%)	0/132 (0.00%)
Interstitial lung disease † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Bronchial fistula † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Hydrothorax † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Pneumonitis † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Pulmonary granuloma † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Pleural fibrosis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Pulmonary fibrosis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Skin and subcutaneous tissue disorders
Dermatitis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Skin ulcer † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Rash † 1	0/611 (0.00%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Vascular disorders
Cardiovascular insufficiency † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Deep vein thrombosis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Hypotension † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Peripheral arterial occlusive disease † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Temporal arteritis † 1	1/611 (0.16%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Aortic aneurysm † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Aortic occlusion † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
Hypertension † 1	0/611 (0.00%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	1/132 (0.76%)
Hypertensive crisis † 1	0/611 (0.00%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	0/132 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (9.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	RC: Erlotinib	RC: Placebo	BPC-NOLC: Erlotinib/Placebo	BPC-NOLC: Placebo Only	BPC-OLC: Erlotinib
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	590/611 (96.56%)	288/343 (83.97%)	125/134 (93.28%)	4/11 (36.36%)	130/132 (98.48%)
Blood and lymphatic system disorders
Anaemia † 1	16/611 (2.62%)	6/343 (1.75%)	2/134 (1.49%)	0/11 (0.00%)	4/132 (3.03%)
Ear and labyrinth disorders
Vertigo † 1	6/611 (0.98%)	6/343 (1.75%)	1/134 (0.75%)	0/11 (0.00%)	4/132 (3.03%)
Eye disorders
Conjunctivitis † 1	34/611 (5.56%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	5/132 (3.79%)
Dry eye † 1	31/611 (5.07%)	3/343 (0.87%)	6/134 (4.48%)	0/11 (0.00%)	5/132 (3.79%)
Eye irritation † 1	8/611 (1.31%)	3/343 (0.87%)	2/134 (1.49%)	0/11 (0.00%)	4/132 (3.03%)
Gastrointestinal disorders
Diarrhoea † 1	318/611 (52.05%)	54/343 (15.74%)	54/134 (40.30%)	0/11 (0.00%)	86/132 (65.15%)
Nausea † 1	84/611 (13.75%)	44/343 (12.83%)	17/134 (12.69%)	1/11 (9.09%)	28/132 (21.21%)
Stomatitis † 1	61/611 (9.98%)	4/343 (1.17%)	8/134 (5.97%)	0/11 (0.00%)	15/132 (11.36%)
Vomiting † 1	55/611 (9.00%)	23/343 (6.71%)	10/134 (7.46%)	0/11 (0.00%)	12/132 (9.09%)
Constipation † 1	35/611 (5.73%)	23/343 (6.71%)	7/134 (5.22%)	0/11 (0.00%)	14/132 (10.61%)
Abdominal pain † 1	34/611 (5.56%)	11/343 (3.21%)	6/134 (4.48%)	0/11 (0.00%)	14/132 (10.61%)
Dyspepsia † 1	30/611 (4.91%)	14/343 (4.08%)	4/134 (2.99%)	0/11 (0.00%)	15/132 (11.36%)
Abdominal pain upper † 1	28/611 (4.58%)	20/343 (5.83%)	0/134 (0.00%)	0/11 (0.00%)	11/132 (8.33%)
Dry mouth † 1	21/611 (3.44%)	3/343 (0.87%)	7/134 (5.22%)	0/11 (0.00%)	7/132 (5.30%)
Gastrooesophageal reflux disease † 1	20/611 (3.27%)	8/343 (2.33%)	1/134 (0.75%)	0/11 (0.00%)	4/132 (3.03%)
Cheilitis † 1	4/611 (0.65%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	8/132 (6.06%)
Mouth ulceration † 1	13/611 (2.13%)	1/343 (0.29%)	1/134 (0.75%)	0/11 (0.00%)	5/132 (3.79%)
Flatulence † 1	11/611 (1.80%)	6/343 (1.75%)	2/134 (1.49%)	0/11 (0.00%)	4/132 (3.03%)
General disorders
Fatigue † 1	118/611 (19.31%)	49/343 (14.29%)	23/134 (17.16%)	0/11 (0.00%)	34/132 (25.76%)
Asthenia † 1	37/611 (6.06%)	21/343 (6.12%)	6/134 (4.48%)	0/11 (0.00%)	6/132 (4.55%)
Mucosal inflammation † 1	27/611 (4.42%)	2/343 (0.58%)	6/134 (4.48%)	0/11 (0.00%)	12/132 (9.09%)
Pyrexia † 1	23/611 (3.76%)	13/343 (3.79%)	6/134 (4.48%)	1/11 (9.09%)	9/132 (6.82%)
Xerosis † 1	19/611 (3.11%)	5/343 (1.46%)	0/134 (0.00%)	0/11 (0.00%)	1/132 (0.76%)
Oedema peripheral † 1	18/611 (2.95%)	11/343 (3.21%)	1/134 (0.75%)	0/11 (0.00%)	5/132 (3.79%)
Chest pain † 1	15/611 (2.45%)	12/343 (3.50%)	2/134 (1.49%)	0/11 (0.00%)	4/132 (3.03%)
Non-cardiac chest pain † 1	12/611 (1.96%)	9/343 (2.62%)	1/134 (0.75%)	0/11 (0.00%)	4/132 (3.03%)
Infections and infestations
Paronychia † 1	39/611 (6.38%)	2/343 (0.58%)	4/134 (2.99%)	0/11 (0.00%)	6/132 (4.55%)
Upper respiratory tract infection † 1	30/611 (4.91%)	15/343 (4.37%)	0/134 (0.00%)	0/11 (0.00%)	13/132 (9.85%)
Nasopharyngitis † 1	29/611 (4.75%)	30/343 (8.75%)	2/134 (1.49%)	0/11 (0.00%)	17/132 (12.88%)
Bronchitis † 1	21/611 (3.44%)	12/343 (3.50%)	1/134 (0.75%)	0/11 (0.00%)	9/132 (6.82%)
Rash pustular † 1	19/611 (3.11%)	1/343 (0.29%)	3/134 (2.24%)	0/11 (0.00%)	13/132 (9.85%)
Urinary tract infection † 1	19/611 (3.11%)	12/343 (3.50%)	1/134 (0.75%)	0/11 (0.00%)	3/132 (2.27%)
Sinusitis † 1	7/611 (1.15%)	8/343 (2.33%)	3/134 (2.24%)	0/11 (0.00%)	7/132 (5.30%)
Ear infection † 1	2/611 (0.33%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	5/132 (3.79%)
Nail infection † 1	2/611 (0.33%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	5/132 (3.79%)
Rhinitis † 1	12/611 (1.96%)	6/343 (1.75%)	1/134 (0.75%)	0/11 (0.00%)	5/132 (3.79%)
Localised infection † 1	4/611 (0.65%)	2/343 (0.58%)	0/134 (0.00%)	0/11 (0.00%)	4/132 (3.03%)
Pneumonia † 1	16/611 (2.62%)	5/343 (1.46%)	1/134 (0.75%)	0/11 (0.00%)	4/132 (3.03%)
Skin infection † 1	3/611 (0.49%)	0/343 (0.00%)	1/134 (0.75%)	0/11 (0.00%)	4/132 (3.03%)
Injury, poisoning and procedural complications
Procedural pain † 1	9/611 (1.47%)	6/343 (1.75%)	4/134 (2.99%)	0/11 (0.00%)	5/132 (3.79%)
Investigations
Weight decreased † 1	56/611 (9.17%)	19/343 (5.54%)	2/134 (1.49%)	0/11 (0.00%)	19/132 (14.39%)
Weight increased † 1	16/611 (2.62%)	20/343 (5.83%)	1/134 (0.75%)	0/11 (0.00%)	6/132 (4.55%)
Blood sodium decreased † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	1/11 (9.09%)	0/132 (0.00%)
Alanine aminotransferase increased † 1	7/611 (1.15%)	6/343 (1.75%)	1/134 (0.75%)	0/11 (0.00%)	4/132 (3.03%)
Metabolism and nutrition disorders
Anorexia † 1	80/611 (13.09%)	24/343 (7.00%)	20/134 (14.93%)	1/11 (9.09%)	20/132 (15.15%)
Dehydration † 1	5/611 (0.82%)	1/343 (0.29%)	4/134 (2.99%)	0/11 (0.00%)	4/132 (3.03%)
Musculoskeletal and connective tissue disorders
Back pain † 1	40/611 (6.55%)	24/343 (7.00%)	3/134 (2.24%)	0/11 (0.00%)	12/132 (9.09%)
Muscle spasms † 1	36/611 (5.89%)	7/343 (2.04%)	1/134 (0.75%)	0/11 (0.00%)	10/132 (7.58%)
Musculoskeletal chest pain † 1	28/611 (4.58%)	10/343 (2.92%)	1/134 (0.75%)	0/11 (0.00%)	3/132 (2.27%)
Arthralgia † 1	23/611 (3.76%)	25/343 (7.29%)	4/134 (2.99%)	0/11 (0.00%)	14/132 (10.61%)
Pain in extremity † 1	23/611 (3.76%)	12/343 (3.50%)	3/134 (2.24%)	0/11 (0.00%)	12/132 (9.09%)
Musculoskeletal pain † 1	20/611 (3.27%)	23/343 (6.71%)	2/134 (1.49%)	0/11 (0.00%)	9/132 (6.82%)
Myalgia † 1	18/611 (2.95%)	6/343 (1.75%)	4/134 (2.99%)	0/11 (0.00%)	6/132 (4.55%)
Nervous system disorders
Headache † 1	42/611 (6.87%)	40/343 (11.66%)	10/134 (7.46%)	0/11 (0.00%)	13/132 (9.85%)
Dizziness † 1	26/611 (4.26%)	22/343 (6.41%)	9/134 (6.72%)	1/11 (9.09%)	13/132 (9.85%)
Dysgeusia † 1	26/611 (4.26%)	4/343 (1.17%)	5/134 (3.73%)	0/11 (0.00%)	13/132 (9.85%)
Paraesthesia † 1	20/611 (3.27%)	15/343 (4.37%)	1/134 (0.75%)	0/11 (0.00%)	0/132 (0.00%)
Lethargy † 1	2/611 (0.33%)	0/343 (0.00%)	0/134 (0.00%)	1/11 (9.09%)	0/132 (0.00%)
Somnolence † 1	4/611 (0.65%)	0/343 (0.00%)	0/134 (0.00%)	1/11 (9.09%)	0/132 (0.00%)
Neuropathy † 1	9/611 (1.47%)	2/343 (0.58%)	1/134 (0.75%)	0/11 (0.00%)	4/132 (3.03%)
Peripheral sensory neuropathy † 1	9/611 (1.47%)	4/343 (1.17%)	2/134 (1.49%)	0/11 (0.00%)	4/132 (3.03%)
Psychiatric disorders
Insomnia † 1	40/611 (6.55%)	21/343 (6.12%)	6/134 (4.48%)	0/11 (0.00%)	16/132 (12.12%)
Depression † 1	33/611 (5.40%)	12/343 (3.50%)	5/134 (3.73%)	0/11 (0.00%)	6/132 (4.55%)
Anxiety † 1	20/611 (3.27%)	14/343 (4.08%)	5/134 (3.73%)	0/11 (0.00%)	7/132 (5.30%)
Aggression † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	1/11 (9.09%)	0/132 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	121/611 (19.80%)	69/343 (20.12%)	17/134 (12.69%)	0/11 (0.00%)	29/132 (21.97%)
Dyspnoea † 1	85/611 (13.91%)	61/343 (17.78%)	15/134 (11.19%)	0/11 (0.00%)	18/132 (13.64%)
Epistaxis † 1	47/611 (7.69%)	4/343 (1.17%)	4/134 (2.99%)	0/11 (0.00%)	11/132 (8.33%)
Haemoptysis † 1	20/611 (3.27%)	4/343 (1.17%)	3/134 (2.24%)	0/11 (0.00%)	4/132 (3.03%)
Rhinorrhoea † 1	19/611 (3.11%)	12/343 (3.50%)	3/134 (2.24%)	0/11 (0.00%)	7/132 (5.30%)
Productive cough † 1	16/611 (2.62%)	14/343 (4.08%)	3/134 (2.24%)	0/11 (0.00%)	6/132 (4.55%)
Pleural fibrosis † 1	0/611 (0.00%)	0/343 (0.00%)	0/134 (0.00%)	1/11 (9.09%)	0/132 (0.00%)
Nasal ulcer † 1	5/611 (0.82%)	0/343 (0.00%)	0/134 (0.00%)	0/11 (0.00%)	5/132 (3.79%)
Pharyngolaryngeal pain † 1	13/611 (2.13%)	8/343 (2.33%)	3/134 (2.24%)	0/11 (0.00%)	5/132 (3.79%)
Dyspnoea exertional † 1	9/611 (1.47%)	9/343 (2.62%)	2/134 (1.49%)	0/11 (0.00%)	4/132 (3.03%)
Skin and subcutaneous tissue disorders
Rash † 1	356/611 (58.27%)	58/343 (16.91%)	51/134 (38.06%)	0/11 (0.00%)	72/132 (54.55%)
Pruritus † 1	161/611 (26.35%)	51/343 (14.87%)	21/134 (15.67%)	0/11 (0.00%)	29/132 (21.97%)
Dry skin † 1	127/611 (20.79%)	50/343 (14.58%)	15/134 (11.19%)	0/11 (0.00%)	41/132 (31.06%)
Dermatitis acneiform † 1	111/611 (18.17%)	19/343 (5.54%)	37/134 (27.61%)	0/11 (0.00%)	45/132 (34.09%)
Alopecia † 1	67/611 (10.97%)	11/343 (3.21%)	12/134 (8.96%)	0/11 (0.00%)	22/132 (16.67%)
Rash erythematous † 1	30/611 (4.91%)	6/343 (1.75%)	6/134 (4.48%)	0/11 (0.00%)	12/132 (9.09%)
Rash maculo-papular † 1	28/611 (4.58%)	3/343 (0.87%)	4/134 (2.99%)	0/11 (0.00%)	7/132 (5.30%)
Skin fissures † 1	26/611 (4.26%)	2/343 (0.58%)	1/134 (0.75%)	0/11 (0.00%)	9/132 (6.82%)
Acne † 1	25/611 (4.09%)	10/343 (2.92%)	6/134 (4.48%)	0/11 (0.00%)	3/132 (2.27%)
Rash papular † 1	25/611 (4.09%)	5/343 (1.46%)	1/134 (0.75%)	0/11 (0.00%)	7/132 (5.30%)
Erythema † 1	24/611 (3.93%)	5/343 (1.46%)	10/134 (7.46%)	0/11 (0.00%)	13/132 (9.85%)
Nail disorder † 1	23/611 (3.76%)	2/343 (0.58%)	1/134 (0.75%)	0/11 (0.00%)	9/132 (6.82%)
Skin exfoliation † 1	23/611 (3.76%)	4/343 (1.17%)	6/134 (4.48%)	0/11 (0.00%)	8/132 (6.06%)
Exfoliative rash † 1	19/611 (3.11%)	2/343 (0.58%)	2/134 (1.49%)	0/11 (0.00%)	11/132 (8.33%)
Blister † 1	8/611 (1.31%)	0/343 (0.00%)	5/134 (3.73%)	0/11 (0.00%)	1/132 (0.76%)
Night sweats † 1	3/611 (0.49%)	0/343 (0.00%)	4/134 (2.99%)	1/11 (9.09%)	1/132 (0.76%)
Rash pruritic † 1	10/611 (1.64%)	1/343 (0.29%)	1/134 (0.75%)	1/11 (9.09%)	5/132 (3.79%)
Dermatitis † 1	4/611 (0.65%)	1/343 (0.29%)	0/134 (0.00%)	0/11 (0.00%)	4/132 (3.03%)
Eczema † 1	11/611 (1.80%)	5/343 (1.46%)	0/134 (0.00%)	0/11 (0.00%)	4/132 (3.03%)
Skin lesion † 1	15/611 (2.45%)	4/343 (1.17%)	1/134 (0.75%)	0/11 (0.00%)	4/132 (3.03%)
Rash macular † 1	18/611 (2.95%)	7/343 (2.04%)	2/134 (1.49%)	0/11 (0.00%)	8/132 (6.06%)
Vascular disorders
Hypertension † 1	22/611 (3.60%)	14/343 (4.08%)	2/134 (1.49%)	0/11 (0.00%)	8/132 (6.06%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (9.1)

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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.

Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 60 days prior to publication for review and comment. Sponsor may delay the publication for up to 6 months to seek patent protection.

Results Point of Contact

• Name/Title: Senior Medical Director, Medical Oncology
• Organization: Astellas Pharma Global Development, Inc.
• EMail: clinicaltrial.disclosure@us.astellas.com

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

Kelly K, Altorki NK, Eberhardt WE, O'Brien ME, Spigel DR, Crino L, Tsai CM, Kim JH, Cho EK, Hoffman PC, Orlov SV, Serwatowski P, Wang J, Foley MA, Horan JD, Shepherd FA. Adjuvant Erlotinib Versus Placebo in Patients With Stage IB-IIIA Non-Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2015 Dec 1;33(34):4007-14. doi: 10.1200/JCO.2015.61.8918. Epub 2015 Aug 31.

• Responsible Party: Astellas Pharma Inc ( OSI Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT00373425
• Other Study ID Numbers: OSI-774-302; 2005-001747-29 ( EudraCT Number )
• First Submitted: September 7, 2006
• First Posted: September 8, 2006
• Results First Submitted: April 2, 2014
• Results First Posted: June 3, 2014
• Last Update Posted: September 17, 2015