Dr Shitara on the Background of the CheckMate 649 Trial in GEJ Adenocarcinoma

Kohei Shitara, MD, medical oncologist, chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, discusses the background of the phase 3 CheckMate 649 study (NCT02872116) investigating nivolumab (Opdivo) plus chemotherapy vs chemotherapy alone in the first-line treatment of patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma.

The CheckMate 649 study was a global trial that established chemotherapy plus nivolumab as the standard treatment for patients with untreated HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinomas. The study successfully met its primary end points of progression-free survival and overall survival benefits with this combination therapy vs chemotherapy alone, as demonstrated in the first interim analysis conducted at a median follow-up of 13.1 months (IQR, 6.7-19.1) for the combination arm vs 11.1 months (IQR, 5.8-16.1) for the chemotherapy alone arm. These findings were published in The Lancet in 2021 and subsequently led to regulatory approval of the regimen in numerous countries. Subsequent analyses, including a 2-year follow-up published in Nature and a 3-year follow-up published in the Journal of Clinical Oncology, have further validated the efficacy of the treatment.

The patient population evaluated in the study consisted of patients in the first-line setting who had not received prior chemotherapy and had confirmed HER2-negative disease, Shitara begins. It is important to note that patients with HER2-positive disease were excluded from the trial, according to Shitara. Beyond this criterion, the trial targeted the usual first-line population for gastric or GEJ adenocarcinomas, he explains. Although a subgroup analysis based on PD-L1 combined positive score was conducted, knowledge of PD-L1 status was not required for inclusion in the all-comer population, Shitara reports.

Overall, the CheckMate 649 study data represent a significant advancement in the treatment paradigm for HER2-negative gastric or GEJ adenocarcinomas, he emphasizes. By establishing the efficacy of chemotherapy plus nivolumab in the first-line setting, the study has provided a new standard of care for patients with this type of cancer, Shitara notes. The inclusion of diverse patient populations and comprehensive follow-up analyses further strengthen the validity and generalizability of the findings, underscoring the importance of this landmark trial in improving patient outcomes, he concludes.