A quality-adjusted time without symptoms and toxicity (Q-TWiST) analysis comparing nivolumab plus ipilimumab (N+I) or nivolumab plus chemotherapy (N+CT) versus CT in patients (pts) with advanced esophageal squamous cell carcinoma (ESCC): CheckMate 648.

Abstract

251 Background: In CheckMate 648, pts with advanced ESCC treated with first-line N+I or N+CT had significantly longer overall survival (OS) vs CT and maintained quality of life (QoL) with no new safety signals. Here we compare between-treatment differences in quality-adjusted survival using a Q-TWiST analysis in all randomized pts (29-month minimum follow-up). Methods: Survival time was partitioned into 3 health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST), and relapse (REL). TOX was defined as time spent with all-cause grade 3/4 adverse events after randomization, prior to disease progression. TWiST was defined as time prior to REL where pts did not experience TOX. REL was defined as time between disease progression and death, or the last known date alive. Mean duration of time in each state was calculated for each treatment group using descriptive statistics and Kaplan-Meier analysis. Utility values from the 3-level EQ-5D (EQ-5D-3L) questionnaire were used to adjust the time spent within each health state for QoL and to calculate Q-TWiST as the utility-weighted sum of the mean health state durations. Bootstrapping (500 samples) was used to estimate time in each health state and to compare mean Q-TWiST estimates between treatments. A between-group difference in Q-TWiST of 5 weeks was prespecified as being clinically important (defined as 10% of OS; based on a median OS in CT group of 10.7 months). Sensitivity analyses were conducted using different combinations of prespecified utility weights for each health state. Results: 970 pts were randomized 1:1:1 to N+I (n = 325), N+CT (n = 321), or CT (n = 324) and included in the Q-TWiST analysis. Median duration of follow-up for survivors was 155 weeks. Mean time in each health state was significantly longer for pts treated with N+I or N+CT compared to CT (Table). Between-group differences in Q-TWiST score were considered clinically important: 5.7 weeks (95% CI 5.5–6.0) favoring N+I vs CT and 7.6 weeks (95% CI 7.4–7.9) favoring N+CT vs CT. Sensitivity analyses supported these findings. Conclusions: In CheckMate 648, pts with unresectable advanced ESCC treated with N+I or N+CT had significantly longer OS compared with those treated with CT. Quality-adjusted survival using Q-TWiST also significantly favored N+I and N+CT compared to CT alone. Pts treated with N+I and N+CT not only experienced increased survival time, but also better QoL during their survival time. Clinical trial information: NCT03143153 . [Table: see text]