The report was published in Journal of Clinical Oncology. The findings add new evidence to the case for the PD-1–targeting monoclonal antibodies in the first-line setting for metastatic NSCLC.
#Keynote 189 trial
Median time to deterioration in cough, chest pain, or dyspnoea was not reached (95% CI 10♲ months to not reached) with pembrolizumab plus pemetrexed–platinum, and was 7♰ months (4♸ months to not reached) with placebo plus pemetrexed–platinum (hazard ratio 0♸1, p=0♱6).New 5-year data from the closely watched KEYNOTE-024 trial (NCT02142738) show pembrolizumab (Keytruda) roughly doubles 5-year overall survival (OS) rates, from 16.3% to 31.9%, versus chemotherapy in patients with metastatic non–small cell lung cancer (NSCLC) with PD-L1 tumor proportion scores (TPS) above 50%. From baseline to week 21, GHS/QOL scores were better maintained with pembrolizumab plus pemetrexed–platinum (least-squares mean change: 1♳ points increase) than with placebo plus pemetrexed–platinum (−4♰ points decrease between-group difference: 5♳ points p=0♰14). From baseline to week 12, GHS/QOL scores were maintained with both pembrolizumab plus pemetrexed–platinum (least-squares mean change: 1♰ point increase) and placebo plus pemetrexed–platinum (−2♶ points decrease between-group difference: 3♶ points p=0♰53). At baseline, 359 (89%) of 402 patients in the pembrolizumab plus pemetrexed–platinum group and 180 (90%) of 200 in the placebo plus pemetrexed–platinum group were compliant with QLQ-C30 at week 12, 319 (90%) of 354 and 149 (89%) of 167 patients were compliant, respectively and at week 21, 249 (76%) of 326 and 91 (64%) of 143 patients were compliant, respectively.
#Keynote 189 pro
402 (99%) of 405 patients in the pembrolizumab plus pemetrexed–platinum group and 200 (99%) of 202 patients in the placebo plus pemetrexed–platinum-treated group completed at least one PRO assessment. This ongoing study is registered with, number NCT02578680.īetween Feb 26, 2016, and March 6, 2017, 616 patients were enrolled median follow-up was 10♵ months (range 0♲–20♴) as of data cutoff on Nov 8, 2017. PROs were analysed in all randomly assigned patients who received at least one dose of study medication and who completed at least one PRO assessment, and the results are provided with two-sided, nominal p values.
Key PRO endpoints were change from baseline to week 12 (during chemotherapy) and week 21 (following chemotherapy) in QLQ-C30 global health status/quality of life (GHS/QOL) score, and time to deterioration in cough, chest pain, or dyspnoea.
The primary endpoints (overall survival and progression-free survival) have been published previously. The European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) and Lung Cancer 13 (QLQ-LC13) were administered at cycles 1–5, every three cycles thereafter during year 1, and every four cycles during years 2–3.
Patients, investigators, and other study personnel were unaware of treatment assignment. Permuted block randomisation (block size six) was done with an interactive voice-response system and stratified by PD-L1 expression, choice of platinum, and smoking status. Patients were randomly assigned (2:1) to receive intravenous pembrolizumab (200 mg) or saline placebo every 3 weeks for up to 2 years (35 cycles) all patients received four cycles of intravenous pemetrexed (500 mg/m 2) with carboplatin (5 mg/mL per min) or cisplatin (75 mg/m 2 investigator's choice) every 3 weeks for four cycles, followed by pemetrexed maintenance therapy every 3 weeks. In the multicentre, double-blind, randomised, placebo-controlled, phase 3 KEYNOTE-189 study done at 126 cancer centres in 16 countries, eligible patients aged 18 years or older with histologically or cytologically confirmed metastatic non-squamous non-small-cell lung cancer without sensitising EGFR or ALK alterations, measurable disease as per Response Evaluation Criteria in Solid Tumors (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled.
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