Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN)

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + EP vs EP in the China cohort was pre-specified at approximately 60% maturity (to ensure a similar maturity to the interim analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP at the China cohort first analysis DCO (06 January 2020), and is comparable in terms of maturity with the interim analysis of OS for D + EP vs EP in the Global cohort. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the China cohort second analysis is presented separately in the subsequent primary outcome measure.

Time frame: From baseline until death due to any cause. Assessed until China cohort first analysis DCO (maximum of approximately 19 months).

Population: The China FAS included all randomized patients in the China cohort. China cohort first analysis for OS was performed for comparison of the D + EP vs EP groups only.

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + T + EP vs EP in the China cohort was pre-specified at approximately 80% maturity (to ensure a similar maturity to the final analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP and D + T + EP vs EP at the time of the China cohort second analysis DCO (02 November 2020), and is comparable in terms of maturity with the final analysis of OS for D + EP vs EP and D + T + EP vs EP in the Global cohort. Analysis of D + EP vs EP at the China cohort first analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (China cohort second analysis) is presented as a secondary outcome measure.

Time frame: From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Population: The China FAS included all randomized patients in the China cohort.

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This primary outcome measure presents OS for the analysis of D + EP vs EP and D + T + EP vs EP at the time of the global cohort final analysis DCO (27 January 2020). Analysis of D + EP vs EP at the global cohort interim analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (global cohort final analysis) is presented as a secondary outcome measure.

Time frame: From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Population: The global FAS included all patients randomized prior to the end of global recruitment.

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An interim analysis of OS in the global cohort was pre-specified after approximately 318 OS events occurred each between the D + EP and EP groups (60% maturity), and between the D + T + EP and EP groups (60% maturity). At the global cohort interim analysis DCO (11 March 2019), comparison of OS in the D + EP versus (vs) EP groups had crossed the pre-specified boundary. Since these results were considered final in terms of formal statistical testing, they are presented here as a primary outcome measure. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the global cohort final analysis is presented separately in the subsequent primary outcome measure.

Time frame: From baseline until death due to any cause. Assessed until global cohort interim analysis DCO (maximum of approximately 23 months).

Population: The global FAS included all patients randomized prior to the end of global recruitment. Interim analysis for OS in the global cohort was performed for comparison of the D + EP vs EP groups only.

The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.

Population: The China FAS included all randomized patients in the China cohort.

The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.

Population: The China FAS included all randomized patients in the China cohort.

A mixed model repeated measures (MMRM) analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as \>75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + T + EP vs P. Analysis of D + EP vs EP is presented in a separate outcome measure.

Time frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Population: The global FAS included all patients randomized prior to the end of global recruitment. For each symptom scale, only patients with data available were included in the analysis.

A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as \>75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + T + EP vs EP. Analysis of D + EP vs EP is presented in a separate outcome measure.

Time frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Population: The China FAS included all randomized patients in the China cohort. For each symptom scale, only patients with data available were included in the analysis.

A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as \>75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + EP vs EP. Analysis of D + T + EP vs EP is presented in a separate outcome measure.

Time frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Population: The China FAS included all randomized patients in the China cohort. For each symptom scale, only patients with data available were included in the analysis.

A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as \>75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + EP vs EP. Analysis of D + T + EP vs EP is presented in a separate outcome measure.

Time frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

Population: The global FAS included all patients randomized prior to the end of global recruitment. For each symptom scale, only patients with data available were included in the analysis.

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to durvalumab for each indicated category.

Time frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the China cohort second analysis DCO (02 November 2020).

Population: The China ADA evaluable patients included those in the China safety analysis set who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. ADA for durvalumab was performed for the D + T + EP and D + EP groups only. The denominator was durvalumab ADA evaluable patients.

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category.

Time frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the China cohort second analysis DCO (02 November 2020).

Population: The China ADA evaluable patients included those in the China safety analysis set who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. ADA for tremelimumab was performed for the D + T + EP group only. The denominator was tremelimumab ADA evaluable patients.

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category.

Time frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the global cohort final analysis DCO (27 January 2020).

Population: The global ADA evaluable patients included those in the global safety analysis set who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. ADA for tremelimumab was performed for the D + T + EP group only. The denominator was tremelimumab ADA evaluable patients.

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of neutralizing antibody (nAb) was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to durvalumab for each indicated category.

Time frame: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the global cohort final analysis DCO (27 January 2020).

Population: The global ADA evaluable patients included those in the global safety analysis set who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result. ADA for durvalumab was performed for the D + T + EP and D + EP groups only. The denominator was durvalumab ADA evaluable patients.

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of patients with at least 1 visit response of Complete Response (CR) or Partial Response (PR). CR was defined as disappearance of all TLs since baseline (any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm) or disappearance of all NTLs since baseline (all lymph nodes must be non-pathological in size \[\<10 mm short axis\]). PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters).

Time frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Population: The global FAS included all patients randomized prior to the end of global recruitment. The denominator was a subset of the FAS population who had measurable disease at baseline.

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of patients with at least 1 visit response of CR or PR. CR was defined as disappearance of all TLs since baseline (any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm) or disappearance of all NTLs since baseline (all lymph nodes must be non-pathological in size \[\<10 mm short axis\]). PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters).

Time frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Population: The China FAS included all randomized patients in the China cohort.

OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months.

Time frame: At 18 months post-randomization. Assessed at the China cohort second analysis DCO (02 November 2020).

Population: The China FAS included all randomized patients in the China cohort.

OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This secondary outcome measure presents OS for the analysis of D + T + EP vs D + EP at the China cohort second analysis DCO (02 November 2020). The alternative treatment comparisons were performed as primary outcome measures.

Time frame: From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Population: The China FAS included all randomized patients in the China cohort.

OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This secondary outcome measure presents OS for the analysis of D + T + EP vs D + EP in the global cohort. The alternative treatment comparisons in the global cohort were performed as primary outcome measures.

Time frame: From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Population: The global FAS included all patients randomized prior to the end of global recruitment.

The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.

Population: The global FAS included all patients randomized prior to the end of global recruitment.

The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.

Population: The global FAS included all patients randomized prior to the end of global recruitment.

OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months.

Time frame: At 18 months post-randomization. Assessed at the global cohort final analysis DCO (27 January 2020).

Population: The global FAS included all patients randomized prior to the end of global recruitment.

PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (ie, PD) was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) and an absolute increase of ≥5 mm for the sum from nadir. For evaluation of NTLs, PD was defined as unequivocal progression of existing NTLs. Median PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Population: The China FAS included all randomized patients in the China cohort.

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.

Time frame: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).

Population: The global PK analysis set included all patients randomized prior to the end of global recruitment who received at least 1 dose of investigational product (IP), per the protocol for whom any post-dose PK data were available. PK for durvalumab was performed for the D + T + EP and D + EP groups only.

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.

Time frame: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).

Population: The China PK analysis set included all patients in the China cohort who received at least 1 dose of IP, per the protocol for whom any post-dose PK data were available. PK for durvalumab was performed for the D + T + EP and D + EP groups only.

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.

Time frame: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).

Population: The China PK analysis set included all patients in the China cohort who received at least 1 dose of IP, per the protocol for whom any post-dose PK data were available. PK for tremelimumab was performed for the D + T + EP group only.

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively.

Time frame: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).

Population: The global PK analysis set included all patients randomized prior to the end of global recruitment who received at least 1 dose of IP, per the protocol for whom any post-dose PK data were available. PK for tremelimumab was performed for the D + T + EP group only.

PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 \[RECIST 1.1\] using Investigator assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (ie, PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir) and an absolute increase of ≥5 millimeters (mm) for the sum from nadir. For evaluation of non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Median PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Population: The global FAS included all patients randomized prior to the end of global recruitment.

The EORTC QLQ-Core 30 version 3 (QLQ-C30 v3) was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.

Time frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Population: The global FAS included all patients randomized prior to the end of global recruitment. For QLQ-C30 function scales and global health status/HRQoL, only patients with baseline scores ≥10 (and with data available) were included in the analysis. For QLQ-C30 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.

The EORTC QLQ-C30 v3 was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.

Time frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Population: The China FAS included all randomized patients in the China cohort. For QLQ-C30 function scales and global health status/HRQoL, only patients with baseline scores ≥10 (and with data available) were included in the analysis. For QLQ-C30 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.

The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and side effects from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (an increase in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.

Time frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Population: The China FAS included all randomized patients in the China cohort. For QLQ-L13 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.

The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and side effects from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (an increase in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration.

Time frame: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Population: The global FAS included all patients randomized prior to the end of global recruitment. For QLQ-L13 symptom scales/items, only patients with baseline scores ≤90 (and with data available) were included in the analysis.