Updated quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of nivolumab plus chemotherapy versus chemotherapy alone as first-line (1L) treatment for advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma (GC/GEJC/EAC): 4-year (yr) follow-up from CheckMate 649 (CM 649).

Daniel Lin Thomas Jefferson University Hospital, Philadelphia, PA info_outline Daniel Lin, Wenying Quan, Marné Garretson, Viktor Chirikov, Clara Chen, Prianka Singh, Catherine Davis, Ryan Sugarman

Authors Daniel Lin Thomas Jefferson University Hospital, Philadelphia, PA info_outline Daniel Lin, Wenying Quan, Marné Garretson, Viktor Chirikov, Clara Chen, Prianka Singh, Catherine Davis, Ryan Sugarman Organizations Thomas Jefferson University Hospital, Philadelphia, PA, OPEN Health, Bethesda, MD, Bristol Myers Squibb, Princeton, NJ, Memorial Sloan Kettering Cancer Center, New York, NY Abstract Disclosures Research Funding Bristol Myers Squibb Background: Q-TWiST analysis is an established methodology combining efficacy, safety, and quality of life (QoL) data into a single metric. Previous analyses among all randomized CM 649 patients with a minimum of 12 months’ follow-up demonstrated that nivolumab plus chemotherapy (NIVO+chemo) yielded a mean Q-TWiST gain of 1.8 (95% CI 0.9-2.7) months, representing an improved 12.8% relative gain, compared with chemo alone (Lin et al, 2023). An updated Q-TWiST analysis using 4-yr follow-up trial data may further inform treatment decisions for patients and providers regarding the long-term benefit of 1L NIVO+chemo in advanced GC/GEJC/EAC. Methods: Overall survival (OS) was partitioned into 3 mutually exclusive 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). Q-TWiST was calculated as the average time spent in each state, weighted by state-specific QoL utility (u, ranging from 0 to 1), assuming a base case u(TOX)=0.5, u(REL)=0.5, u(TWiST)=1. In sensitivity analysis (SA), utility values derived from the trial’s treatment-specific UK EQ-5D-3L scores reported during each state were instead used. Relative Q-TWiST gains were calculated by dividing the NIVO+chemo Q-TWiST difference versus chemo by the mean chemo group OS where gains ≥ 10% or ≥ 15% were considered “clinically important” or “clearly clinically important” (1). Results: With a minimum of 48 months of follow-up (and maximum of 66 months), patients on NIVO+chemo had a mean Q-TWiST gain of 3.4 months (1.8-5.1) compared with chemo alone, translating to a 20.5% relative Q-TWiST gain. In SA, using the trial’s treatment-specific EQ-5D-3L utility values resulted in an even greater mean Q-TWiST gain of 3.8 months (2.5-5.3) and 23% relative gain. Both base case and SA results were clearly clinically important. Relative gain benefit of NIVO+chemo (15.7%) remained clearly clinically important after broadening the analysis to include grade 2 adverse events, as well. Conclusions: This updated Q-TWiST analysis using 4-yr follow-up CM 649 data among all randomized patients demonstrates the clearly clinically important long-term benefit of NIVO+chemo versus chemo in advanced GC/GEJC/EAC. Compared with the originally published Q-TWiST findings with 12 months of follow-up, this update highlights that both the absolute and relative Q-TWiST gains in favor of NIVO+chemo are almost double with longer observed follow-up. These findings continue to support the use of 1LNIVO+chemo in advanced GC/GEJC/EAC. 1. Solem et al, 2018. Clinical trial information: NCT02872116.

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