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

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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Posted on 19 November 202121 May 2024