Trial Outcomes & Findings for A Study of Tarceva (Erlotinib) in Combination With Gemcitabine in Unresectable and/or Metastatic Cancer of the Pancreas: Relationship Between Skin Toxicity and Survival (NCT NCT00461708)

NCT ID: NCT00461708

Last Updated: 2015-10-15

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 153 participants
• Primary outcome timeframe: Enrollment through Cycle 24 (4-week cycles), up to 24 months.
• Results posted on: 2015-10-15

Participant Flow

Participant milestones

Measure	Erlotinib, Gemcitabine: Rash Grade Less Than (<) 2 Participants with a rash Grade \< 2 according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version (V) 3.0 received erlotinib, 100 milligrams (mg), orally (PO), once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 milligrams per square meter (mg/m\^2), intravenously (IV), over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade Greater Than/Equal to (≥) 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Overall Study STARTED	115	38
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	115	38

Reasons for withdrawal

Measure	Erlotinib, Gemcitabine: Rash Grade Less Than (<) 2 Participants with a rash Grade \< 2 according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version (V) 3.0 received erlotinib, 100 milligrams (mg), orally (PO), once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 milligrams per square meter (mg/m\^2), intravenously (IV), over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade Greater Than/Equal to (≥) 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Overall Study Adverse Event	17	7
Overall Study Lack of Efficacy	68	20
Overall Study Physician Decision	10	4
Overall Study Withdrawal by Subject	8	2
Overall Study Other	4	4
Overall Study Death	8	1

Baseline Characteristics

A Study of Tarceva (Erlotinib) in Combination With Gemcitabine in Unresectable and/or Metastatic Cancer of the Pancreas: Relationship Between Skin Toxicity and Survival

Baseline characteristics by cohort

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=115 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=38 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Total n=153 Participants Total of all reporting groups
Age, Continuous	63.6 years STANDARD_DEVIATION 9.9 • n=5 Participants	62.0 years STANDARD_DEVIATION 10.6 • n=7 Participants	63.2 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	10 Participants n=7 Participants	71 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	28 Participants n=7 Participants	82 Participants n=5 Participants

PRIMARY outcome

Timeframe: Enrollment through Cycle 24 (4-week cycles), up to 24 months.

Population: ITT population

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=115 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=38 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Number of Participants Who Died During the Study	102 participants	27 participants	—

PRIMARY outcome

Timeframe: Enrollment through Cycle 24 (4-week cycles), up to 24 months.

Population: ITT population; only participants who died were included in the analysis.

OS was defined as the time, in months, from the date of enrollment to the date of death due to any cause. Participants whose last recorded status was not death were censored. OS was estimated using Kaplan-Meier methodology.

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=102 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=27 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Overall Survival (OS) During the Study	4.468 months Interval 3.618 to 5.318	10.546 months Interval 9.679 to 11.414	—

SECONDARY outcome

Timeframe: Enrollment through Cycle 6 (4-week cycles), up to 6 months.

Population: ITT population

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=115 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=38 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Number of Participants Who Died at 6 Months	69 participants	8 participants	—

SECONDARY outcome

Timeframe: Enrollment through Cycle 6 (4-week cycles), up to 6 months.

Population: ITT population; only participants who died were included in the analysis.

OS was defined as the time, in months, from the date of enrollment to the date of death due to any cause. Participants whose last recorded status was not death were censored. OS was estimated using Kaplan-Meier methodology.

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=69 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=8 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
OS At 6 Months	4.468 months Interval 3.618 to 5.318	NA months The median and 95% confidence interval could not be calculated because of the large number of censored events.	—

SECONDARY outcome

Timeframe: Enrollment through Cycle 24 (4-week cycles), up to 24 months.

Population: ITT population

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=71 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=44 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=38 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Number of Participants Who Died During the Study By Rash Grade	65 participants	37 participants	27 participants

SECONDARY outcome

Timeframe: Enrollment through Cycle 24 (4-week cycles), up to 24 months.

Population: ITT population; only participants who died were included in the analysis.

OS was defined as the time, in months, from the date of enrollment to the date of death due to any cause. Participants whose last recorded status was not death were censored. OS was estimated using Kaplan-Meier methodology.

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=65 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=37 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=27 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
OS By Rash Grade	3.318 months Interval 2.446 to 4.191	6.571 months Interval 5.139 to 8.003	10.546 months Interval 9.679 to 11.414

SECONDARY outcome

Timeframe: Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months.

Population: ITT population

Progression-free survival (PFS) was defined as the time from the date of enrollment to the date of document disease progression or death due to any cause. As per Response Evaluation Criteria in Solid Tumors (RECIST) V 1.0, progressive disease (PD) was defined for target lesions (TLs) as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded since the start of treatment, and for non-target lesions (NTLs) as unequivocal progression of NTLs. Participants whose last recorded status was not PD or death were censored.

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=115 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=38 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Number of Participants With Disease Progression or Death	110 participants	33 participants	—

SECONDARY outcome

Timeframe: Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months

Population: ITT population; only participants with an event (death or disease progression) were included in the analysis.

The time, in months, from enrollment to PFS event. Participants whose last recorded status was not progression or death were censored. PFS was estimated using Kaplan-Meier methodology.

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=110 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=33 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
PFS	2.497 months Interval 2.13 to 2.864	6.439 months Interval 4.919 to 7.96	—

SECONDARY outcome

Timeframe: Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months.

Population: ITT population

As per RECIST V 1.0: for TLs, a CR was defined as the disappearance of all TLs; and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline (BL) SLD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Participants for whom no assessment of response was available and who had finalized the study due to disease progression or tumor-related death, disease progression was considered the BOR.

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=115 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=38 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST	7.0 percentage of participants	21.1 percentage of participants	—

SECONDARY outcome

Timeframe: Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months.

Population: ITT population

Disease control was defined as BOR of CR, PR, or stable disease (SD). As per RECIST V 1.0: for TLs, a CR was defined as the disappearance of all TLs; and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD was defined as the persistence of one or more NTLs and/or maintenance of tumor marker level above the normal limits. Participants for whom no assessment of response was available and who had finalized the study due to disease progression or tumor-related death, disease progression was considered the BOR.

Outcome measures

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=115 Participants Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=38 Participants Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Percentage of Participants With Disease Control According to RECIST	42.6 percentage of participants	84.2 percentage of participants	—

Adverse Events

Erlotinib, Gemcitabine: Rash Grade < 2

Serious events: 58 serious events

Other events: 115 other events

Deaths: 0 deaths

Erlotinib, Gemcitabine: Rash Grade ≥ 2

Serious events: 14 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=115 participants at risk Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=38 participants at risk Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Gastrointestinal disorders Haemorrhage, GI	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign prostatic hyperplasia	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Gastrointestinal toxicity	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Anaemia	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Back pain	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Cardiac disorders Pericardial effusion	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Vomiting	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Sudden death	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Hepatobiliary disorders Bilirubin (Hyperbilirubinemia)	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Haemorrhage, rectal	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Surgical and medical procedures Liver	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Myelosuppression	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Thrombocytopenia	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Cardiac disorders Cardiac failure congestive	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Hypertension	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Cardiac disorders Left ventricular dysfunction	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Cardiac disorders Valvular heart disease	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Fatigue	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Fever	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Investigations Weight loss	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Diarrhea	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Gastrointestinal syndrome	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Obstruction, GI	9.6% 11/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Perforation, GI	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Visceral arterial ischemia	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders Haemorrhage, CNS	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Hepatobiliary disorders Liver dysfunction	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Hepatobiliary disorders Liver dysfunction/failure	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Pancreatitis	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Anal/perianal	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Blood	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Cellulitis	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Lung (pneumonia)	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	7.9% 3/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Peritoneal cavity	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Upper airway nos	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Urinary tract nos	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders CNS Cerebrovascular ischemia	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Psychiatric disorders Confusion	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders Speech impairment	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Abdomen nos	4.3% 5/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Renal and urinary disorders Obstruction, GU	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Renal and urinary disorders Renal failure	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Thrombosis/Embolism	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Thrombosis/Thrombus	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Visceral arterial ischemia	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Pain	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Diabetes	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.

Other adverse events

Measure	Erlotinib, Gemcitabine: Rash Grade < 2 n=115 participants at risk Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.	Erlotinib, Gemcitabine: Rash Grade ≥ 2 n=38 participants at risk Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant.
Infections and infestations Middle ear	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Nausea	37.4% 43/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	31.6% 12/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Constipation	33.0% 38/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	31.6% 12/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Vomiting	29.6% 34/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	21.1% 8/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Neutropenia	17.4% 20/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	42.1% 16/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Anorexia	53.9% 62/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	28.9% 11/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Investigations Weight loss	23.5% 27/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	13.2% 5/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Fever	15.7% 18/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	28.9% 11/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Fatigue	77.4% 89/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	81.6% 31/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders Dysgeusia	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	13.2% 5/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Ascites	6.1% 7/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Psychiatric disorders Insomnia	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Flatulence	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Eye disorders Cataract	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Psychiatric disorders Confusion	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Muscle weakness	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Oral cavity	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Esophagitis	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Hypertension	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Pulmonary hypertension	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Myelitis	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Rhinitis	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders Tremor	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Arthritis	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Dysphagia	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Gastritis	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Lymphopenia	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders Neuropathy	5.2% 6/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Obesity	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Eye disorders Eyelid dysfunction	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Eye disorders Ocular surface disease	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Chills	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Cardiac disorders Atrial fibrillation	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Haematoma	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Hypotension	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Monocytopenia	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Proctitis	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Immune system disorders Allergic reaction	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Thrombocytosis	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Eye disorders Vision - Blurred vision	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Immune system disorders Allergy /immunology- other	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Ear and labyrinth disorders Hearing loss	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Anaemia	27.8% 32/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	28.9% 11/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Granulocytopenia	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Hemoglobin	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Hemorrhage	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Leukocytes	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Leukocytosis	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Leukopenia	7.0% 8/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	7.9% 3/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Cardiac disorders Left ventricular dysfunction	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Constitutional symptoms- other	9.6% 11/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	15.8% 6/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Sweating	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Skin and subcutaneous tissue disorders Cheilitis	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Skin and subcutaneous tissue disorders Dermatology/skin- other	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Skin and subcutaneous tissue disorders Hypopigmentation	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Skin and subcutaneous tissue disorders Nail changes	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Skin and subcutaneous tissue disorders Pruritus/itching	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Skin and subcutaneous tissue disorders Rash/desquamation	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Diabetes	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Endocrine disorders Endocrine- other	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Diarrhea	47.8% 55/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	39.5% 15/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Gastrointestinal - other	18.3% 21/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	13.2% 5/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Gastrointestinal toxicity	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Heartburn/dyspepsia	11.3% 13/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	7.9% 3/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Hemorrhoids	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Mucositis/stomatitis	16.5% 19/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	23.7% 9/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Obstruction, GI	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Perforation, GI	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Periodontal disease	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Xerostomia	5.2% 6/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Anal haemorrhage	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Hemorrhage nasal	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Hemorrhage rectal	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Hepatobiliary disorders Liver dysfunction	7.0% 8/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	7.9% 3/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Pancreas, exocrine	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Abdomen nos	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Anal/perianal	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Blood	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Conjunctiva	4.3% 5/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Infection	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Lung (Pneumonia)	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Oral cavity-gums	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Skin	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Soft tissue nos	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Upper airway nos	5.2% 6/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	7.9% 3/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Urinary tract nos	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Edema	9.6% 11/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	7.9% 3/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Edema: limb	19.1% 22/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Lymphatics- other	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Albumin, serum-low	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Investigations Alkaline phosphatase	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Investigations ALT, SGPT	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Hepatobiliary disorders Bilirubin	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	10.5% 4/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Calcium, serum high	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Investigations GGT (Gamma-glutamyl)	4.3% 5/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Glucose, serum high	5.2% 6/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Glucose, serum low	4.3% 5/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Hypercreatinaemia	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Magnesium, serum low	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Metabolic/laboratory	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Potassium, serum high	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Metabolism and nutrition disorders Potassium, serum low	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders Dizziness	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders Extrapyramidal	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Psychiatric disorders Personality/behavioral	16.5% 19/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders Somnolence	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Other	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Abdomen nos	67.8% 78/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	50.0% 19/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Back	7.8% 9/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	18.4% 7/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Bone	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Chest/thorax nos	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Renal and urinary disorders Genitourinary	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Nervous system disorders Headache	5.2% 6/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Joint	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Renal and urinary disorders Kidney	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Muscle	4.3% 5/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	15.8% 6/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Neck	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Musculoskeletal and connective tissue disorders Neck/back	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Pain	15.7% 18/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	21.1% 8/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Peritoneum	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Skin	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
General disorders Nasal/ paranasal	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Nasal/paranasal reactions	5.2% 6/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	10.5% 4/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Cough	10.4% 12/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	10.5% 4/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.6% 11/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	13.2% 5/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Hiccoughs	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Pulmonay/upper respiratoy- other	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Voice changes	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Infections and infestations Cystitis	5.2% 6/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	5.3% 2/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Renal and urinary disorders Incontinence, urinary	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Renal and urinary disorders Renal failure	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Renal and urinary disorders Renal/genitourinary	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Reproductive system and breast disorders Testicular oedema	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Renal and urinary disorders Urinary retention	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Renal and urinary disorders Urine color change	5.2% 6/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Surgical and medical procedures Upper airway nos	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Surgical and medical procedures Vein nos	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Phlebitis	4.3% 5/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	10.5% 4/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Thrombosis/embolism	6.1% 7/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	13.2% 5/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Thrombosis/thrombus	3.5% 4/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Vascular disorders Vein injury	0.00% 0/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	2.6% 1/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Gastrointestinal disorders Distension/bloating	2.6% 3/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	7.9% 3/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Injury, poisoning and procedural complications Fracture	0.87% 1/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Eye disorders Ocular/visual- other	1.7% 2/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	0.00% 0/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.
Blood and lymphatic system disorders Thrombopenia	18.3% 21/115 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.	26.3% 10/38 • Adverse events (AEs) were recorded at every study visit for up to a maximum of 24 treatment cycles. All participants who received at least 1 dose of study treatment were included in the safety analysis.

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER