A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of patients in CheckMate 649: Nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC).

Abstract

273 Background: In CheckMate 649 (CM 649), a randomized phase 3 trial of first-line treatment of advanced GC/GEJC/EAC, patients receiving nivolumab combined with chemotherapy (NIVO plus chemo) experienced superior overall survival (OS), progression-free survival (PFS), and maintained their HRQOL for longer duration versus chemo alone. In this analysis, we combined efficacy and HRQOL data from CM-649 into a single metric, quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST), to compare the net benefits of NIVO plus chemo versus chemo alone. Methods: In this analysis, OS was partitioned into three health states: time with grade 3/4 toxicity after randomization and before progression (TOX), time without symptoms of disease progression or toxicity (TWiST), and time from relapse or progression until death (ie, relapse, REL). Mean Q-TWiST was determined by multiplying each state’s duration with its utility (U) (U[TWiST], 1.0; U[TOX], 0.5; U[REL], 0.5). Relative Q-TWiST gains (calculated as Q-TWiST difference divided by chemo only OS) of ≥ 10% and ≥ 15% were defined as clinically important and clearly clinically important, respectively, based on established thresholds for clinical importance in prior Q-TWiST literature. Q-TWiST differences between treatments were calculated separately for patients whose tumors expressed PD-L1 CPS ≥ 5 and for all randomized. A threshold utility analysis assessed Q-TWiST differences by varying the TOX and REL utility between 0 and 1. Results: Compared with chemo alone, treatment with NIVO plus chemo was associated with Q-TWiST improvement of 2.8 months (95% CI 1.0-3.7; relative gain 20.6% [clearly clinically important]) in patients with PD-L1 CPS ≥ 5, and 1.8 months (95% CI 0.9-2.7; relative gain 12.7% [clinically important]) in all randomized patients, respectively. Threshold analyses showed that compared with chemo alone, treatment with NIVO plus chemo was associated with statistically significant Q-TWiST improvements exceeding minimum clinically important differences across the full range of TOX and REL utility values. Conclusions: Among previously untreated patients with GC/GEJC/EAC in CM-649, NIVO plus chemo significantly improved quality-adjusted survival compared with chemo alone. Q-TWiST gains with NIVO plus chemo were driven mostly by longer time patients experienced without symptoms of disease progression or toxicity (TWiST), and were associated with statistically significant and clinically meaningful gains. These Q-TWiST results provide further understanding of both a survival and quality of life benefit of NIVO plus chemo versus chemo alone, and may aid clinicians and patients in management decisions for this patient population.