Brahmer JR, et al. - In this study, researchers sought to report the prespecified exploratory endpoint of pembrolizumab vs chemotherapy on patient-reported outcomes (PROs) in advanced, programmed cell death-ligand 1 (PD-L1)-positive non-small-cell lung cancer (NSCLC). Compared with chemotherapy, pembrolizumab was superior in improving or maintaining health-related quality-of-life (QOL). Thereby suggesting that it might represent a new first-line standard of care for PD-L1-expressing, advanced NSCLC.

Methods

• Researchers performed a multicentre, international, randomised, open-label, phase 3 trial.
• This trial included patients with treatment-naive, stage IV NSCLC in 102 sites in 16 countries.
• Measurable disease (per RECIST version 1.1) and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 were evident in eligible patients.
• They randomly assigned patients (1:1) via an interactive voice response system and integrated web response system to receive either pembrolizumab 200 mg every 3 weeks (35 cycles) or investigator-choice platinum-doublet chemotherapy (4–6 cycles or until documented disease progression or unacceptable toxicity).
• Based on geography, ECOG performance status, and histology, they stratified randomisation.
• At day 1 of cycles 1–3, every 9 weeks thereafter, at the treatment discontinuation visit, and at the 30-day safety assessment visit, they assessed PROs using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), the EORTC Quality of Life Questionnaire Lung Cancer 13 items (QLQ-LC13), and the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) questionnaire.
• In this study, the key exploratory PRO endpoints (analysed for all patients who received at least one dose of study treatment and completed at least one PRO instrument at at least one timepoint) included baseline-to-week-15 change in the QLQ-C30 global health status (GHS)/quality-of-life (QOL) score and time to deterioration of the composite of cough, chest pain, and dyspnoea in the QLQ-LC13.

Results

• Researchers randomly assigned 305 patients to pembrolizumab (n=154) or chemotherapy (n=151) from Sept 19, 2014, to Oct 29, 2015.
• They identified 3 patients in each group who did not complete any PRO instruments at any timepoints, and thus included 299 patients in the full analysis set.
• In each group, 1 of these patients did not complete any PRO instruments before week 15, and so were not included in analyses of change from baseline to week 15.
• At baseline, PRO compliance was greater than 90% and at week 15, it was approximately 80% for both groups.
• In QLQ-C30 GHS/QOL score, least-squares mean baseline-to-week-15 change was 6·9 (95% CI 3·3 to 10·6) for pembrolizumab and -0·9 (-4·8 to 3·0) for chemotherapy, for a difference of 7·8 (2·9 to 12·8; two-sided nominal p=0·0020).
• Pembrolizumab-treated patients indicated fewer deterioration in the QLQ-LC13 composite endpoint than did chemotherapy-treated patients (46 [31%] of 151 patients vs 58 [39%] of 148 patients).
• With pembrolizumab, time to deterioration was longer than with chemotherapy (median not reached [95% CI 8·5 to not reached] vs 5·0 months [3·6 to not reached]; hazard ratio 0·66, 95% CI 0·44-0·97; two-sided nominal p=0·029).