First-line treatment of gastric, gastroesophageal junction (GEJ), and esophageal cancers with nivolumab plus chemotherapy prolonged progression-free survival (PFS) and overall survival (OS) compared with chemotherapy alone, according to interim results of the phase 3 CheckMate 649 trial presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.1
“Nivolumab plus chemotherapy represents a new potential standard first-line treatment for patients with advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma cancers,” Markus Moehler, MD, PhD, of the Johannes Gutenberg-Universität Mainz in Germany, and presenter of the study, said.
The international phase 3 CheckMate 649 trial randomly assigned 1581 patients with unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma cancers to receive nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy alone. Chemotherapy was either oxaliplatin plus capecitabine (XELOX; 51.5%) or leucovorin, 5-flurouracil, and oxaliplatin (FOLFOX; 48.5%). The coprimary endpoints were OS and PFS among patients with PD-L1 tumor expression of combined positive score (CPS) of 5 or higher. Secondary endpoints included objective response rate (ORR), and OS and PFS in all randomized patients.
The median patient age at baseline was 63 years, and 71% of patients were male. Approximately one-quarter of patients were Asian. Most tumors were gastric cancer (70%), followed by GEJ (18%), and esophageal adenocarcinoma (13%). Most patients had metastatic disease (96% and few patients had tumors with high microsatellite instability (4%).
The present interim analysis was for the nivolumab plus chemotherapy and chemotherapy alone groups.
Among patients with a PD-L1 CPS of 5 or higher, the ORR was significantly higher in the nivolumab plus chemotherapy group at 60% compared with 45% with chemotherapy, with a duration of response of 9.5 and 7.0 months, respectively.
Nivolumab plus chemotherapy significantly prolonged survival, with a median OS of 14.4 months compared with 11.1 months with chemotherapy alone (hazard ratio [HR], 0.71; 98.4% CI, 0.59-0.86; P <.0001) among patients with a PD-L1 CPS of 5 or more. This benefit was consistent among patients with a PD-L1 CPS 1 or higher (HR, 0.77; 99.3% CI, 0.64-0.92; P =.0001) and all randomized patients (HR, 0.80; 99.3% CI, 0.68-0.94; P =.0002).
Nivolumab plus chemotherapy also improved PFS, with a median of 7.7 months compared with 6 months with chemotherapy alone (HR, 0.68; 98.0% CI, 0.56-0.81; P <.0001) among patients with a PD-L1 CPS of at least 5. Treatment with nivolumab plus chemotherapy also improved PFS among patients with a PD-L1 CPS of 1 or higher (HR, 0.74; 95% CI, 0.65-0.85) and all randomized patients (HR, 0.77; 95% CI, 0.68-0.87).
OS favored nivolumab plus chemotherapy over chemotherapy alone across all subgroups.
Grade 3 to 4 treatment-related adverse events (TRAEs) occurred in 59% of patients in the nivolumab plus chemotherapy arm and 44% of patients in the chemotherapy arm, which led to treatment discontinuations among 36% and 24% of patients, respectively.
Dr Moehler said the following in a press release: “The open question is the effect in patients who have a PD-L1 CPS <5.” Ongoing analyses will evaluate subgroups and other biomarkers to better characterize the benefit of nivolumab plus chemotherapy.2
Disclosure: Some of the authors of the study reported financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.
- Moehler M, Shitara K, Garrido M, et al. Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. Presented at: European Society of Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract LBA6_PR.
- European Society of Medical Oncology (ESMO). Immunotherapy is beneficial in gastric and oesophageal cancers, studies show [press release]. Published September 21, 2020. Accessed September 21, 2020.
This article originally appeared on Cancer Therapy Advisor