Pembrolizumab monotherapy showed significantly longer progression-free survival and overall survival (OS), and fewer treatment-related adverse events (AEs) compared to chemotherapy in patients with metastatic non-small cell lung cancer (mNSCLC) with PD-L1 positive tumors in the first-line setting (KEYNOTE-024 (KN024)) and in those previously treated (KEYNOTE-010 (KN010)). The objective of this analysis is to assess the benefit-risk of pembrolizumab in terms of quality-adjusted survival amongst patients in these trials.
The Quality-adjusted Time without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare the trial arms. Survival time of each patient was partitioned into three health states: with toxicity before disease progression, without toxicity before disease progression, and disease progression until death. Toxicities considered were grade 3+ AEs. Mean utility scores for the three health states were estimated using EQ-5D-3L data collected in the trials. Q-TWiST was calculated as the utility-weighted sum of the mean health state durations. KN024 and KN010 have undergone several interim analyses. Data from each of these analyses were examined. The published criterion [Revicki 2006] for a ‘clearly clinically important’ improvement in Q-TWiST is 15% of mean OS in a study.
Based on the most recent analysis of KN024 from July 10, 2017 and KN010 from March 24, 2017, patients randomized to pembrolizumab had 3.25 months (about 20% of mean OS) greater Q-TWiST (P < 0.001) compared to those randomized to platinum-based chemotherapy in KN024, and 3.11 months (about 25% of mean OS) greater Q-TWiST (P < 0.001) compared to docetaxel in KN010. Results across KN024 and KN010 trial analyses showed an increase in trend for the Q-TWiST improvement of pembrolizumab over time.
Pembrolizumab showed statistically significant and clinically meaningful improvement in quality-adjusted survival using the Q-TWiST analysis compared to chemotherapy in mNSCLC in both previously untreated and treated patients. The benefits continued to accrue over the trial follow-up period with extended survival.
Clinical trial identification
Legal entity responsible for the study
Merck & Co. Inc.
Merck & Co. Inc.
M. Huang, M.C. Pietanza, A. Samkari, J. Pellissier, T. Burke, S. Chandwani, F. Kong: Employee: Merck & Co., Inc. A.S. Pickard: Consulting fees: Merck, Eli Lilly, Bristol-Myers Squibb, Novartis/Avexis.