Opinion

Video

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

Yelena Y. Janjigian, MD, presents 4-year follow-up data from the CheckMate 649 study investigating frontline nivolumab plus chemotherapy in patients with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma.

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.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.
Related Videos
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, on progression patterns and subsequent therapies after lorlatinib in ALK-positive NSCLC.
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, discuss preclinical CNS data for the ROS1 inhibitor zidesamtinib.
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, discuss data for zidesamtinib in ROS1-positive non–small cell lung cancer.
Mohammed Najeeb Al Hallak, MD, MS, and Sakti Chakrabarti, MD, discuss ongoing research in gastrointestinal cancers.
Mohammed Najeeb Al Hallak, MD, MS, and Sakti Chakrabarti, MD, discuss research building upon approved combinations in unresectable hepatocellular carcinoma.
Mohammed Najeeb Al Hallak, MD, MS, and Sakti Chakrabarti, MD, on trastuzumab deruxtecan–based regimens in advanced HER2-positive GI cancers.
Mohammed Najeeb Al Hallak, MD, MS, and Sakti Chakrabarti, MD, on tremelimumab/durvalumab vs atezolizumab/bevacizumab in unresectable HCC.
Mohammed Najeeb Al Hallak, MD, MS, and Sakti Chakrabarti, MD, on 5-year data for tremelimumab plus durvalumab in unresectable HCC.
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, discuss data for NVL-655 in ALK-positive NSCLC and other ALK-positive solid tumors.
Gregory J. Riely, MD, PhD, and Benjamin Besse, MD, discuss testing for ALK-positive and ROS1-positive non–small cell lung cancer.