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CheckMate-649: Survival Outcome Improved in Patients with Advanced Gastric/Esophageal Cancer Treated with Nivolumab Combined with Chemotherapy

2021 Year in Review - Gastrointestinal Cancer

Nivolumab combined with chemotherapy had improved survival outcomes and an acceptable safety profile in patients with advanced gastric/esophageal cancer, according to CheckMate-649 study results.

The fourth leading cause of cancer death globally is gastric cancer.1 The most common type of gastric and gastroesophageal junction (GEJ) cancer is adenocarcinoma.1 Treatment of gastric and GEJ cancer with chemotherapy yields comparable treatment outcomes.1 For advanced or metastatic unresectable HER2-negative GEJ or gastric adenocarcinoma, the standard first-line treatment is fluoropyrimidine plus platinum-based chemotherapy.1 Despite this treatment, there is a poor median overall survival (OS) of <1 year.1

At the European Society for Medical Oncology Congress 2021, Janjigian and colleagues presented follow-up study information on nivolumab plus chemotherapy versus chemotherapy alone and initial results on the combination of nivolumab plus ipilimumab versus chemotherapy alone. Patient enrollment was allowed regardless of PD-L1 expression, but patients who had HER2-positive status were excluded from the study. Primary end points were OS and progression-free survival (PFS).

The study enrolled 1581 patients who were randomized to receive nivolumab plus chemotherapy or chemotherapy alone. A PD-L1 combined positive score (CPS) ≥5 was found in 60% of the patients. Nivolumab was dosed at 360 mg every 3 weeks or 240 mg every 2 weeks. The chemotherapy regimen was capecitabine and oxaliplatin (XELOX) every 3 weeks or fluorouracil, leucovorin, and oxaliplatin (FOLFOX) every 2 weeks. Patients treated with nivolumab plus chemotherapy had continued improvement in OS over the 12-month study follow-up period when compared with chemotherapy alone (hazard ratio, 0.71; 98.4% confidence interval, 0.59-0.86; P <.0001). There was also a 3.3-month improvement in median OS in patients with PD-L1 CPS ≥5 and a superior PFS in this patient subgroup, with a 32% reduction in risk for death or progression compared with the chemotherapy group. An acceptable safety profile was found for treatment with nivolumab plus chemotherapy.

There were 813 participants enrolled, who were randomized to receive nivolumab plus ipilimumab or chemotherapy alone. PD-L1 CPS ≥5 was found in 58% of these patients. Nivolumab was dosed at 1 mg/kg and ipilimumab was dosed at 3 mg/kg every 3 weeks for 4 doses and then nivolumab at 240 mg every 2 weeks. Analysis of the data revealed nivolumab plus ipilimumab did not confer any significant OS benefit when compared with chemotherapy.

Nivolumab plus chemotherapy demonstrated a safe, clinically meaningful long-term survival benefit when compared with chemotherapy, including in patients who were PD-L1 expressors and nonexpressors.

In April 2021, nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy was approved by the FDA in all comers (both PD-L1 expressors and nonexpressors) with advanced gastric cancer, GEJ cancer, and esophageal adenocarcinoma.

Source: Janjigian YY, Ajani JA, Moehler M, et al. Nivolumab (NIVO) plus chemotherapy (chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): CheckMate 649 study. Ann Oncol. 2021;32(suppl_5):S1283-S1346.


  1. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398:27-40.
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