Abstract 399P
Background
In CheckMate 648, pts with advanced ESCC treated with first-line N+CT or N+I demonstrated significant survival benefit vs CT, and quality-adjusted survival favored N+CT or N+I in the all-randomized population. Here we compare between-treatment differences in quality-adjusted survival using Q-TWiST analysis in those randomized pts with tumor cell PD-L1 expression ≥ 1% (29-month minimum follow-up).
Methods
Survival time was partitioned into three health states: (1) progression (PROG), defined as time between disease progression and death (or last known alive date); (2) toxicity (TOX), defined as time from randomization to PROG spent with all-cause grade 3-4 adverse events; and (3) time without symptoms of disease progression or toxicity (TWiST), defined as time from randomization to PROG where pts did not experience TOX. Duration of time in each state was calculated using Kaplan-Meier methods. Utility values derived from the EQ-5D-3L assessments administered during study were used to calculate Q-TWiST as the utility-weighted sum of health state durations. Bootstrapping (500 samples) was used to estimate and to compare Q-TWiST between treatments. A between-group difference in Q-TWiST of 1 month (based on 10% of the median OS difference) was pre-specified as clinically important.
Results
473 (49%) of pts had tumor cell PD-L1 expression ≥ 1% (N+CT: 158, N+I: 158, CT: 157) and were included in the Q-TWiST analysis. Between-group differences in Q-TWiST score were clinically important: 3.3 months (95% CI: 1.7, 4.9) favoring N+CT vs CT and 3.2 months (95% CI: 1.6, 4.9) favoring N+I vs CT. Table: 399P
| Mean (95% CI) (months) | |||
| N+CT (n=158) | N+I (n=158) | CT (n=157) | |
| Q-TWiST | 11.5 (10.2, 13.0) | 11.4 (10.0, 12.8) | 8.2 (7.2, 9.2) |
| TOX time | 1.5 (0.9, 2.2) | 1.0 (0.7, 1.4) | 0.7 (0.5, 0.9) |
| TWiST time | 7.9 (6.4, 9.5) | 7.4 (5.4, 9.1) | 4.8 (4.0, 5.6) |
| PROG time | 7.8 (6.4, 9.2) | 8.4 (6.7, 10.1) | 6.3 (5.0, 7.4) |
Conclusions
Quality-adjusted survival using Q-TWiST methodology significantly favored both N+CT and N+I compared to CT alone, further supporting N+CT and N+I as 1L treatment options for advanced ESCC pts with tumor cell PD-L1 ≥ 1%.
Clinical trial identification
NCT03143153.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
I. Chau: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eli Lilly, MSD, Roche, Merck Serono, AstraZeneca, OncXerna, Astella, Incyte, GSK, Sotio, Daiichi Sankyo, Eisai, Taiho, Seagen, Turning Point Therapeutics, Novartis, Takeda, Elevation Oncology; Financial Interests, Personal, Invited Speaker: Eisai, Eli Lilly, Servier, Roche; Financial Interests, Institutional, Invited Speaker: Cilag-Janssen, Eli Lilly. J.A. Bridgewater: Financial Interests, Personal, Advisory Board: Taiho, BMS, Incyte, Basilea, Servier; Financial Interests, Personal, Other, Advisor: AstraZeneca; Financial Interests, Institutional, Funding: Incyte. L.S. Wyrwicz: Financial Interests, Personal, Other, Honoraria: BeiGene, BMS, MSD; Financial Interests, Personal, Advisory Board: GSK, Servier; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Other, Travel, Accommodations Expenses: Servier. M. Greenwood: Financial Interests, Personal, Full or part-time Employment: Adelphi Values PCOO. S.I. Blum: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: GSK. F. Taylor: Financial Interests, Personal, Full or part-time Employment: Adelphi Values, a consultancy firm that has received payment from BMS to conduct analysis of HRQoL data from BMS's clinical trials: Adelphi Values. C. Davis, P. Singh: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. All other authors have declared no conflicts of interest.