KEY TAKEAWAYS
- The CheckMate 648 phase III trial aimed to assess the treatment disparities in quality-adjusted survival via Q-TWiST analysis among ESCC patients.
- The results demonstrated that unresectable advanced ESCC patients treated with N+I or N+CT had prolonged OS and improved QoL.
In CheckMate 648, patients with advanced esophageal squamous cell carcinoma (ESCC) receiving first-line treatment with N+I or N+CT demonstrated markedly extended overall survival (OS) compared to CT, alongside sustained quality of life (QoL) without any novel safety concerns.
Ian Chau and the team aimed to analyze inter-treatment variances in quality-adjusted survival through Q-TWiST assessment among all randomized patients, with a minimum follow-up of 29 months.
The study categorized survival time into three health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST), and relapse (REL). TOX included the duration with all-cause grade 3/4 adverse events (AEs) post-randomization until disease progression. TWiST represented the period before REL where patients did not experience TOX. REL was defined as the interval between disease progression and death or last known date alive. Mean durations in each state were computed for each treatment group via descriptive statistics and Kaplan-Meier analysis. Utility values from the EQ-5D-3L questionnaire were utilized to adjust time spent in each health state for QoL, and to compute Q-TWiST as the utility-weighted sum of mean health state durations.
Bootstrapping (500 samples) was employed to estimate time in each health state and compare mean Q-TWiST estimates between treatments. A between-group difference in Q-TWiST of 5 weeks was pre-specified as clinically significant (10% of OS, based on a median OS in CT group of 10.7 months). Sensitivity analyses were conducted using different combinations of pre-specified utility weights for each health state.
About 970 patients were randomized in a 1:1:1 ratio to receive N+I (n = 325), N+CT (n = 321), or CT (n = 324), all of whom were included in the Q-TWiST analysis. The median follow-up duration for survivors was 155 weeks. Patients treated with N+I or N+CT experienced significantly longer mean durations in each health state compared to those receiving CT.. Between-group differences in Q-TWiST scores were clinically notable: 5.7 weeks (95% CI 5.5–6.0) in favor of N+I vs. CT and 7.6 weeks (95% CI 7.4–7.9) in favor of N+CT vs. CT. Sensitivity analyses provided further support for these results.
The study found that the unresectable advanced ESCC patients treated with N+I or N+CT exhibited notably prolonged OS compared to those treated with CT alone. Additionally, quality-adjusted survival using Q-TWiST favored N+I and N+CT, highlighting improved outcomes and better QoL. Research was funded by Bristol-Myers Squibb.
Source: https://meetings.asco.org/abstracts-presentations/229139
Clinical Trial: https://clinicaltrials.gov/study/NCT03143153
Chau I, Bridgewater JA, Wyrwicz L, et al. (2024). “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.” Presented at ASCO GI 2024 10.1200/JCO.2024.42.3_suppl.251 (251).
