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Consistent benefit of anti-PD-1 therapy for oesophageal and gastric cancer

Presented By
Dr Yelena Janjigian, Memorial Sloan Kettering Cancer Center, NY, USA
ESMO 2021
Phase 3, CheckMate649
Updated results from the CheckMate649 study report continued overall survival (OS) benefit of nivolumab/chemotherapy versus chemotherapy alone in patients with advanced gastric cancer (GC)/gastroesophageal junction cancer (GEJC)/oesophageal adenocarcinoma (EAC). In contrast, there was no OS benefit with nivolumab/ipilimumab versus chemotherapy.

Recently, results from the randomised, global, phase 3 CheckMate649 study (NCT02872116) demonstrated superior OS with first-line nivolumab/chemotherapy versus chemotherapy in patients with advanced GC/GEJC/EAC, leading to FDA approval [1]. Dr Yelena Janjigian (Memorial Sloan Kettering Cancer Center, NY, USA) presented updated results from CheckMate649 with longer follow-up for nivolumab/chemotherapy versus chemotherapy and first results for nivolumab/ipilimumab versus chemotherapy [2].

In CheckMate649, 2,031 patients with previously untreated, unresectable advanced or metastatic GC/GEJC/EAC were enrolled regardless of PD-L1 expression. Patients with known HER2-positive status were excluded. Patients were randomised to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks)/chemotherapy (XELOX every 3 weeks or FOLFOX every 2 weeks) (n=789), nivolumab (1 mg/kg)/ipilimumab (3 mg/kg every 3 weeks, 4 doses, then nivolumab 240 mg every 2 weeks) (n=409), or chemotherapy alone (n=833). Dual primary endpoints were OS and progression-free survival (PFS) per blinded independent central review for nivolumab/chemotherapy versus chemotherapy in patients with PD-L1 combined positive score (CPS) ≥5 (n=955). Hierarchically tested secondary endpoints included OS in nivolumab/chemotherapy versus chemotherapy in patients with CPS ≥1 (n=1,581) and OS in nivolumab/ipilimumab versus chemotherapy (CPS ≥5, n=473).

Nivolumab/chemotherapy continued to show improvement in OS versus chemotherapy alone with an additional 12 months of follow-up from the primary analysis: median OS was 14.4 months versus 11.1 months (HR 0.70) in CPS ≥5 patients and 13.8 months versus 11.6 months (HR 0.79) in all randomised patients. 2-year OS rates were 31% versus 19% (CPS ≥5), and 28% versus 19% (all randomised). Median OS in microsatellite instability-high (MSI-H) patients (n=44) was 38.7 months versus 12.3 months (HR 0.38).

The secondary endpoint of OS in patients with CPS ≥5 for nivolumab/ipilimumab versus chemotherapy was not met (11.2 vs 11.6 months; HR 0.89). Median OS in MSI-H patients (n=21) was not reached versus 10.0 months (HR 0.28). No new safety signals were identified.

“These updated results from CheckMate649 continue to demonstrate clinically meaningful long-term survival benefit from first-line nivolumab/chemotherapy versus chemotherapy alone and an acceptable safety profile,” concluded Dr Janjigian. “This further supports the use of nivolumab/chemotherapy as a new standard first-line treatment in patients with advanced GC/GEJC/EAC, with best benefit in CPS ≥5 patients.”

  1. Janjigian YY, et al. Lancet 2021;398:27-40.

  2. Janjigian YY, et al. Nivolumab (NIVO) plus chemotherapy (Chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment foradvanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): CheckMate649 study. Abstract LBA7, ESMO Congress 2021, 16–21 September.


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