CheckMate-649: 5-year follow up data

The pivotal, phase III CheckMate-649 established the combination of nivolumab and chemotherapy as the new standard of care first line treatment for patients with advanced gastric (GC), gastro-esophageal junction (GEJ) or esophageal (EAC) cancer. In this video, Prof Em Eric Van Cutsem, digestive oncologist at the University Hospitals Leuven and Prof Yelena Janjigian, medical oncologist at Memorial Sloan Lettering Cancer Center in New York, discuss the 5-year follow-up data of this study as presented during ASCO GI 2025.

In CheckMate-649, 2,032 patients with previously untreated, unresectable, advanced or metastatic, non-HER2+ GC/GEJC/EAC were randomized to nivolumab (NIVO) + chemotherapy (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemotherapy alone. The 5-year data of this trial confirmed earlier findings with a significantly better overall survival (OS) for patients treated with NIVO + chemotherapy versus chemotherapy alone (median OS: 13.7 vs. 11.6 months; HR[95%CI]: 0.79[0.71-0.88]). As already described in earlier reports of this trial, the OS benefit obtained by adding NIVO became more pronounced with increasing levels of PD-L1 expression. In the subgroup of patients with a PD-L1 CPS of ≥5 (the EMA approved population for this combination), the median OS with NIVO + chemotherapy and chemotherapy alone were reported at 14.4 and 11.1 months, respectively (HR[95%CI]: 0.71[0.61-0.81]). At 60 months, this translated into an OS rate of 16% for NIVO + chemotherapy as compared to 6% with chemotherapy alone.

Prior to the immunochemotherapy era, the survival prospect for patients with advanced GC/GEJ/EAC was very dismal at less than a year. These updated results now show that, depending on the disease biology, patients have about 15% chance of being alive after 5 years. Unfortunately, however, there are currently no clinical biomarkers that can help in identifying these patients. In the video, Prof Van Cutsem and Prof Janjigian also address the issue of the optimal treatment duration of immunotherapy in this setting. While CheckMate-649 restricted the nivolumab treatment to 2 years, it proves to be very difficult to convince patients to stop the nivolumab in clinical practice.