KEY TAKEAWAYS
- The CheckMate 649 phase 3 trial aimed to investigate the superior OS and PFS of NIVO + chemo in untreated advanced non-HER2+ GC/GEJC/EAC patients.
- The primary endpoint was to determine PFS and OS.
- Researchers noticed that NIVO + chemo, a pioneering PD-1 inhibitor/chemo combo, exhibits sustained efficacy and safety for previously untreated advanced GC/GEJC/EAC patients.
Nivolumab (NIVO) + chemotherapy (chemo) proved superior overall survival (OS) and clinically meaningful progression-free survival (PFS) in advanced non-HER2+, gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC), leading to approvals in many countries. NIVO + chemo demonstrated clinically meaningful improvement in efficacy at 2—and 3-year follow-ups.
Kohei Shitara and the team aimed to assess long-term outcomes, presenting 4-year results from CheckMate 649, solidifying NIVO + chemo as a pivotal 1L treatment.
They conducted an inclusive analysis enrolling adults with previously untreated, unresectable advanced, or metastatic GC/GEJC/EAC, irrespective of programmed death ligand 1 (PD-L1) expression. HER2+ patients were excluded. Randomized participants received NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. The dual primary endpoints for NIVO + chemo vs chemo included OS and progression-free survival (PFS) by blinded independent central review (BICR) in patients with PD-L1 combined positive score (CPS) ≥ 5.
About 1581 patients underwent randomization into NIVO + chemo or chemo arms. At the 48-month minimum follow-up, NIVO + chemo demonstrated sustained OS and progression-free survival (PFS) benefits compared to chemo in patients with PD-L1 CPS ≥ 5 and across all randomized patients. Notably, OS benefits with NIVO + chemo were evident in most prespecified subgroups. Objective response rates (ORR) were higher, and responses exhibited increased durability with NIVO + chemo versus chemo in PD-L1 CPS ≥ 5 and all randomized patients.
In an exploratory analysis of OS at the 18-week landmark, numerically more patients achieved response with NIVO + chemo compared to chemo. Median OS (95% CI) with NIVO + chemo was numerically longer in responders versus non-responders for both PD-L1 CPS ≥ 5 (20.5 [17.5–25.0] vs 14.0 [11.6–15.7]) and all randomized patients (19.4 [17.5–21.7] vs 13.1 [11.6–14.4]). No new safety signals emerged, consistent with the 3-year follow-up.
The study concluded that NIVO + chemo, the pioneering PD-1 inhibitor/chemo combination, showcases sustained efficacy and acceptable safety over a 4-year follow-up, reinforcing its position as a standard 1L treatment for previously untreated advanced GC/GEJC/EAC.
The study is sponsored by Bristol-Myers Squibb
Source: https://meetings.asco.org/abstracts-presentations/229157
Clinical Trial: https://clinicaltrials.gov/study/NCT02872116
Shitara K, Moehler M H, Ajani J A, et al. (2024). “Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 4 year (yr) follow-up of CheckMate 649.” Presented at ASCO GI 2024 (Abstract 306).
