Nivolumab Plus Chemotherapy vs Chemotherapy as First-Line Treatment for Advanced Gastric Cancer/Gastroesophageal Junction Cancer/Esophageal Adenocarcinoma: 4-Year Follow-Up of the CheckMate 649 Study

Background

• Standard first line (1L) chemotherapy (chemo) for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) results in poor median overall survival (OS) of < 1 year1-4
• NIVO + chemo demonstrated superior OS and clinically meaningful PFS benefit vs chemo and an acceptable safety profile after 1 year of follow-up in previously untreated, non-HER2-positive patients with advanced GC/GEJC/esophageal adenocarcinoma (EAC) in CheckMate 6495
• NIVO + chemo is currently approved in ˃ 50 countries as 1L treatment for patients with advanced or metastatic GC/GEJC/EAC6-9
• NIVO + chemo continued to demonstrate clinically meaningful improvement in efficacy vs chemo with an acceptable safety profile after 2 and 3 years of follow-up10,11
• We report 4-year follow-up results from the NIVO + chemo vs chemo arms of CheckMate 649

Methods

• CheckMate 649 (NCT02872116) is a randomized, open-label, global phase 3 study (Figure 1)
• Patients were enrolled from 175 hospitals and cancer centers in 29 countries

Results

• At data cutoff (May 29, 2023), the minimum follow-up (time from concurrent randomization of the last patient to clinical data cutoff) was 48.1 months
• Three patients in the NIVO + chemo arm and 9 patients in the chemo arm were receiving ongoing treatment (chemo only) at data cutoff
• The distribution of baseline characteristics was consistent with that of patients with PD-L1 CPS ≥ 5
• Clinically meaningful improvement in OS with NIVO + chemo vs chemo was maintained with longer follow-up in PD-L1 CPS ≥ 5, PD-L1 CPS ≥ 1, and all randomized populations
• NIVO + chemo continued to demonstrate PFS benefit with longer follow-up vs chemo in PD-L1 CPS ≥ 5, PD-L1 CPS ≥ 1, and all randomized populations
• OS consistently favored NIVO + chemo vs chemo with longer follow-up across multiple prespecified subgroups in patients with PD-L1 CPS ≥5
• OS benefit with NIVO + chemo was enriched at higher PD-L1 CPS cutoffs
• ORR was higher with NIVO + chemo vs chemo across all PD-L1 CPS subgroups
• Higher ORR was maintained, and responses remained more durable with NIVO + chemo vs chemo with longer follow-up

Conclusions

• NIVO + chemo is the first PD-1 inhibitor plus chemo combination to demonstrate long-term efficacy vs chemo and acceptable safety after 4 years of follow-up in previously untreated patients with advanced GC/GEJC/EAC
  • Clinically meaningful OS benefit, with sustained separation of the Kaplan‑Meier curves
  • PFS benefit in PD-L1 CPS ≥ 5, PD-L1 CPS ≥ 1, and all randomized populations
  • OS benefit across all subgroups and enriched at higher PD-L1 CPS cutoffs
  • Higher ORR across all evaluated PD-L1 CPS subgroups
  • Favorable PFS2
  • Longer median OS in the exploratory landmark analysis of responders vs non‑responders
• No new safety signals were identified with longer follow-up
• Efficacy benefit with NIVO + chemo was maintained with longer follow-up further supporting its use as standard 1L treatment in patients with advanced GC/GEJC/EAC

Shitara K, Moehler M, Ajani J et al. Nivolumab plus chemotherapy vs chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma: 4-year follow-up of the CheckMate 649 study. Presented at: 2024 ASCO Gastrointestinal Cancers Symposium, January 18-20, 2024. San Francisco, California.

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