Trial Outcomes & Findings for A Study of First-line Maintenance Erlotinib Versus Erlotinib at Disease Progression in Participants With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Platinum-Based Chemotherapy (NCT NCT01328951)

Last Updated: 2016-10-28

Results Overview

Participants were followed for survival until death or premature withdrawal. The percentage of participants who died during the Overall Study (BP, OLP, or SFU) was calculated.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

643 participants

Primary outcome timeframe

Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death)

Results posted on

2016-10-28

Participant Flow

The study consisted of three periods: a Blinded Phase (BP), an Open-Label Phase (OLP), and final Survival Follow-Up (SFU). These periods were not necessarily sequential, because the OLP could be "skipped" in select participants. Therefore, the reasons for discontinuation are presented altogether within the Overall Study.

Participant milestones

Participant milestones
Measure	Late Erlotinib Participants received blinded placebo tablets orally (PO) once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not epidermal growth factor receptor \[EGFR\] targeted therapies) or best supportive care (BSC) as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Overall Study STARTED	321	322
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	321	322

Reasons for withdrawal

Reasons for withdrawal
Measure	Late Erlotinib Participants received blinded placebo tablets orally (PO) once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not epidermal growth factor receptor \[EGFR\] targeted therapies) or best supportive care (BSC) as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Overall Study Disease Progression	17	14
Overall Study Adverse Event	2	0
Overall Study Death	243	258
Overall Study Lost to Follow-up	6	7
Overall Study Withdrawal by Subject	6	6
Overall Study Study Closed by the Sponsor	36	31
Overall Study Other	11	6

Baseline Characteristics

A Study of First-line Maintenance Erlotinib Versus Erlotinib at Disease Progression in Participants With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Platinum-Based Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Total n=643 Participants Total of all reporting groups
Age, Continuous	60.6 years STANDARD_DEVIATION 9.1 • n=93 Participants	60.8 years STANDARD_DEVIATION 8.8 • n=4 Participants	60.7 years STANDARD_DEVIATION 8.9 • n=27 Participants
Sex: Female, Male Female	77 Participants n=93 Participants	84 Participants n=4 Participants	161 Participants n=27 Participants
Sex: Female, Male Male	244 Participants n=93 Participants	238 Participants n=4 Participants	482 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP; per local standards during OLP; then every 12 weeks during SFU until death)

Population: ITT Population.

Participants were followed for survival until death or premature withdrawal. The percentage of participants who died during the Overall Study (BP, OLP, or SFU) was calculated.

Outcome measures

Outcome measures
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Percentage of Participants Who Died During the Overall Study	73.2 percentage of participants	75.2 percentage of participants

PRIMARY outcome

Population: ITT Population.

Participants were followed for survival until death or premature withdrawal. OS was defined as the interval between date of randomization and date of death from any cause. Median time to event during the Overall Study (BP, OLP, or SFU) was estimated using the Kaplan-Meier method and expressed in months.

Outcome measures

Outcome measures
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Overall Survival (OS) as Median Time to Event During the Overall Study	9.46 months Interval 8.38 to 11.33	9.72 months Interval 8.57 to 11.17

PRIMARY outcome

Timeframe: At 1 year

Population: ITT Population.

Participants were followed for survival until death or premature withdrawal. The percentage of participants event-free (i.e., still alive) at 1 year during the Overall Study was calculated.

Outcome measures

Outcome measures
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Percentage of Participants Event-Free (Alive) at 1 Year During the Overall Study	41.75 percentage of participants Interval 36.2 to 47.3	42.15 percentage of participants Interval 36.6 to 47.7

SECONDARY outcome

Timeframe: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)

Population: ITT Population.

Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Disease progression was defined as a greater than or equal to (≥) 20 percent (%) and ≥5-millimeter (mm) increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. The percentage of participants who died or experienced disease progression during the BP was calculated.

Outcome measures

Outcome measures
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Percentage of Participants Who Died or Experienced Disease Progression During Blinded Treatment	95.0 percentage of participants	94.1 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)

Population: ITT Population.

Tumor response was evaluated using RECIST version 1.1. Disease progression was defined as a ≥20% and ≥5-mm increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. PFS was defined as the interval between date of randomization and date of first documented death or disease progression. Median time to event during the BP was estimated using the Kaplan-Meier method and expressed in weeks.

Outcome measures

Outcome measures
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Progression-Free Survival (PFS) as Median Time to Event During Blinded Treatment	12.00 weeks Interval 11.71 to 12.29	13.00 weeks Interval 12.14 to 17.43

SECONDARY outcome

Timeframe: At 6 months

Population: ITT Population.

Tumor response was evaluated using RECIST version 1.1. Disease progression was defined as a ≥20% and ≥5-mm increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. The percentage of participants event-free (i.e., still alive and without disease progression) at 6 months during the BP was calculated.

Outcome measures

Outcome measures
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Percentage of Participants Event-Free (Alive and No Disease Progression) at 6 Months During Blinded Treatment	24.22 percentage of participants Interval 19.5 to 28.94	27.11 percentage of participants Interval 22.19 to 32.02

SECONDARY outcome

Timeframe: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)

Population: ITT Population.

Tumor response was evaluated using RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and short-axis reduction to less than (\<) 10 mm of any pathological lymph nodes. PR was defined as a ≥30% decrease in the sum of target lesion diameters in reference to the Baseline sum. The percentage of participants with a best overall response of either CR or PR (i.e., the objective response rate \[ORR\]) during the BP was calculated, and corresponding 95% CI was constructed using the Pearson-Clopper method.

Outcome measures

Outcome measures
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to RECIST During Blinded Treatment	3.7 percentage of participants Interval 1.95 to 6.44	6.5 percentage of participants Interval 4.08 to 9.8

SECONDARY outcome

Timeframe: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)

Population: ITT Population.

Tumor response was evaluated using RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and short-axis reduction to \<10 mm of any pathological lymph nodes. PR was defined as a ≥30% decrease in the sum of target lesion diameters in reference to the Baseline sum. Stable disease (SD) was defined as neither sufficient shrinkage in target lesions to qualify for PR nor sufficient growth to qualify for disease progression. Disease progression (progressive disease/PD) was defined as a ≥20% and ≥5-mm increase in the sum of target lesion diameters in reference to the smallest sum on study and/or substantial worsening in non-target disease. The percentage of participants with each level of best tumor response during the BP was calculated, and corresponding 95% CI was constructed using the Pearson-Clopper method.

Outcome measures

Outcome measures
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Percentage of Participants by Best Overall Response According to RECIST During Blinded Treatment CR	0.6 percentage of participants Interval 0.08 to 2.23	0.9 percentage of participants Interval 0.19 to 2.7
Percentage of Participants by Best Overall Response According to RECIST During Blinded Treatment PR	3.1 percentage of participants Interval 1.5 to 5.65	5.6 percentage of participants Interval 3.35 to 8.69
Percentage of Participants by Best Overall Response According to RECIST During Blinded Treatment SD	55.5 percentage of participants Interval 49.83 to 60.97	54.7 percentage of participants Interval 49.04 to 60.19
Percentage of Participants by Best Overall Response According to RECIST During Blinded Treatment PD	38.6 percentage of participants Interval 33.27 to 44.2	32.3 percentage of participants Interval 27.22 to 37.71
Percentage of Participants by Best Overall Response According to RECIST During Blinded Treatment Missing	2.2 percentage of participants Interval 0.88 to 4.44	6.5 percentage of participants Interval 4.08 to 9.8

SECONDARY outcome

Timeframe: Up to approximately 3.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until/at disease progression during BP)

Population: ITT Population.

Tumor response was evaluated using RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and short-axis reduction to \<10 mm of any pathological lymph nodes. PR was defined as a ≥30% decrease in the sum of target lesion diameters in reference to the Baseline sum. SD was defined as neither sufficient shrinkage in target lesions to qualify for PR nor sufficient growth to qualify for disease progression. The percentage of participants with a best overall response of CR, PR, or SD (i.e., the disease control rate \[DCR\]) during the BP was calculated, and corresponding 95% CI was constructed using the Pearson-Clopper method.

Outcome measures

Outcome measures
Measure	Late Erlotinib n=321 Participants Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive second-line erlotinib tablets during the OLP as 150 mg PO once daily, provided by the Sponsor. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.	Early Erlotinib n=322 Participants Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity. Those who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator during the OLP. This treatment continued until disease progression, death, or unacceptable toxicity. If disease progression or unacceptable toxicity occurred during the OLP, the participant entered a final SFU period. Participants could also enter the SFU period directly after the BP if they were unable to receive second-line treatment per protocol.
Percentage of Participants With CR, PR, or SD According to RECIST During Blinded Treatment	59.2 percentage of participants Interval 53.59 to 64.62	61.2 percentage of participants Interval 55.62 to 66.53

Adverse Events

Placebo (Late Erlotinib)

Serious events: 27 serious events

Other events: 107 other events

Deaths: 0 deaths

Erlotinib (Early Erlotinib)

Serious events: 36 serious events

Other events: 206 other events

Deaths: 0 deaths

Second-Line Erlotinib (Late Erlotinib)

Serious events: 23 serious events

Other events: 1 other events

Deaths: 0 deaths

Second-Line Chemotherapy (Early Erlotinib)

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo (Late Erlotinib) n=319 participants at risk Participants received blinded placebo tablets PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity.	Erlotinib (Early Erlotinib) n=322 participants at risk Participants received blinded erlotinib tablets, 150 mg PO once daily during the BP in the maintenance setting until disease progression, death, or unacceptable toxicity.	Second-Line Erlotinib (Late Erlotinib) n=1 participants at risk；n=248 participants at risk Participants who received blinded placebo and who demonstrated disease progression were unblinded and could receive second-line erlotinib as 150-mg tablets PO once daily, provided by the Sponsor. This treatment continued during the OLP until disease progression, death, or unacceptable toxicity.	Second-Line Chemotherapy (Early Erlotinib) n=162 participants at risk Participants who received blinded erlotinib and who demonstrated disease progression were unblinded and could receive an approved second-line therapy (but not EGFR targeted therapies) or BSC as chosen by the investigator. This treatment continued during the OLP until disease progression, death, or unacceptable toxicity.
Gastrointestinal disorders Diarrhoea	4.4% 14/319 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	24.2% 78/322 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.
General disorders Chest pain	3.4% 11/319 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	5.3% 17/322 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.
General disorders Fatigue	6.3% 20/319 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	6.5% 21/322 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.
Metabolism and nutrition disorders Decreased appetite	3.4% 11/319 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	6.5% 21/322 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.
Respiratory, thoracic and mediastinal disorders Cough	11.6% 37/319 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	9.6% 31/322 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.2% 23/319 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	8.4% 27/322 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.
Skin and subcutaneous tissue disorders Pruritus	0.94% 3/319 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	5.3% 17/322 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.
Skin and subcutaneous tissue disorders Rash	10.0% 32/319 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	39.4% 127/322 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	100.0% 1/1 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.94% 3/319 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	5.3% 17/322 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.	— 0/0 • Up to approximately 4.5 years (visits at Baseline and Weeks 6, 12, and 18 and every 12 weeks until disease progression, death, or unacceptable toxicity during BP; per local standards and 28 days after last visit during OLP) Safety Population: All participants who received at least one dose of study treatment, according to drug actually received. Non-serious adverse events (NSAEs) were not collected in the OLP. Hence, 0 participants would be affected and at risk in "Other (Not Including Serious) Adverse Events". However, an NSAE in 1 participant was reported to Roche outside protocol (see "Rash"). Other NSAEs that may have occurred during the OLP are not included in the table because they were not reported to Roche.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

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