KEY TAKEAWAYS
- This phase 3 randomized clinical trial, known as CheckMate 649, evaluates the efficacy and safety of NIVO + chemo in previously untreated patients with EAC, GEJC, and Advanced Gastric Cancer.
- NIVO + chemo improved survival in CPS ≥5 patients regardless of PD-L1 expression.
- The ORR was higher in patients treated with NIVO + chemo, and responses were more durable than those treated with chemo alone.
- The benefits of NIVO + chemo were observed across most prespecified subgroups, and no new safety signals were identified.
- After 3 years of follow-up, NIVO + chemo demonstrated clinically meaningful long-term survival benefits and is a standard first-line treatment in previously untreated patients with EAC, GEJC, and Advanced Gastric Cancer.
In untreated patients with advanced gastric cancer (GC), gastroesophageal junction cancer (GEJC), esophageal adenocarcinoma (EAC), NIVO with chemotherapy showed better overall survival (OS) and clinically relevant progression-free survival (PFS) benefit vs. chemotherapy with an acceptable safety profile, leading to approval in various countries, including the United States. After 2 years of follow-up, the clinically relevant improvement in efficacy shown with NIVO + chemo persisted. They compared the effectiveness and safety of NIVO plus chemotherapy against chemotherapy over 3 years, using data from the CheckMate 649 trial.
Without respect to programmed death ligand 1 (PD-L1) expression status, adults with untreated progressed or metastatic GC/GEJC/EAC were enrolled. Those who were already known to be HER2-positive were not considered. Patients in this study were randomly assigned to receive either NIVO (360 mg Q3W or 240 mg Q2W) Plus chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. In patients with a PD-L1 combined positive score (CPS) of 5, the primary outcomes of NIVO plus chemotherapy versus chemotherapy were overall survival (OS) and progression-free survival (PFS) as assessed by blinded independent central review (BICR). Altogether, 581 pts were randomly assigned to either NIVO + chemo or chemo.
Those with PD-L1 CPS 5 and all randomized patients continued to benefit from NIVO + chemo in terms of overall survival (OS) and progression-free survival (PFS) with a minimum of 36 months (mo) of follow-up. Those with PD-L1 CPS 5 and detectable lesions at baseline had a 60% (95% CI 55-65) ORR per BICR with NIVO + chemo compared to a 45% (95% CI 40-50) ORR with chemo; in all randomized patients, the ORR per BICR with NIVO + chemo was 58% (95% CI 54-62) compared to a 46% (95% CI 42-50) ORR In patients with PD-L1 CPS 5, the mDOR was 9.6 months (95% CI 8.2-12.4) with NIVO + chemo compared to 7.0 months (95% CI 5.6-7.9) with chemo alone, and in all randomized patients, the mDOR was 8.5 months (95% CI 7.7-9.9) with NIVO + chemo compared to 6.9 months (95% CI 5.8-7.2) with chemo alone.
Overall survival was improved with NIVO + chemo in most predicted subgroups. There were no unforeseen warning signs found. An overview of treatment-associated side effects is presented. About 3 years after treatment, patients with advanced GC/GEJC/EAC without prior treatment showed a clinically significant long-term survival advantage with an acceptable safety profile when treated with NIVO + chemo.
Source: https://meetings.asco.org/abstracts-presentations/215801
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02872116/
Janjigian, Y.Y., Shitara, K., Moehler, M.H., Garrido, M., Gallardo, C., Shen, L., Yamaguchi, K., Wyrwicz, L., Skoczylas, T., Campos Bragagnoli, A.S., Liu, T., Tehfe, M., Elimova, E., Bruges Maya, R.E., Cleary, J.M., Karamouzis, M., Soleymani, S., Lei, M., Amaya-Chanaga, C. and Ajani, J.A. (2023). Nivolumab (NIVO) plus chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 3-year follow-up from CheckMate 649. Journal of Clinical Oncology, 41(4_suppl), pp.291–291. doi:https://doi.org/10.1200/jco.2023.41.4_suppl.291.
