Pembrolizumab plus chemotherapy for advanced gastric cancer

Adding immune checkpoint inhibitors such as nivolumab and sintilimab to standard chemotherapy has been reported to improve survival in patients with HER2-negative advanced gastric adenocarcinoma. 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 Summary Full Text Full Text PDF PubMed Google Scholar , 2 Xu J Jiang H Pan Y et al. Abstract CT078: first-line treatment with sintilimab (sin) vs placebo in combination with chemotherapy (chemo) in patients (pts) with unresectable gastric or gastroesophageal junction (G/GEJ) cancer: final overall survival (OS) results from the randomized, phase III ORIENT-16 trial. Cancer Res. 2023; 83 (CT078): CT078 Google Scholar However, the value of adding pembrolizumab to standard chemotherapy is unknown. We read with great interest the Article by Sun Young Rha and colleagues in The Lancet Oncology. 3 Rha SY Oh D-Y Yañez P et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023; 24: 1181-1195 Summary Full Text Full Text PDF PubMed Google Scholar The authors found that pembrolizumab plus chemotherapy significantly improved the overall survival and progression-free survival for patients with HER2-negative advanced gastric cancer compared with placebo plus chemotherapy. We do however have some questions and suggestions. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trialParticipants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma. Full-Text PDF Pembrolizumab plus chemotherapy for advanced gastric cancer – Authors' replyThe letter from Chen-yu Huang and Xiao-bing Wu raises questions pertaining to the survival results from the recent analysis of the KEYNOTE-859 study published in The Lancet Oncology.1 The authors suggest that the efficacy of addition of pembrolizumab to chemotherapy versus placebo plus chemotherapy might be affected by the choice of chemotherapy, type of post-discontinuation anticancer therapy, and the level of expression of PD-L1. Full-Text PDF Pembrolizumab plus chemotherapy for advanced gastric cancerIn The Lancet, Yelena Y Janjigian and colleagues1 recently published the results of the interim analyses of the KEYNOTE-811 trial, comparing first-line pembrolizumab plus trastuzumab and chemotherapy with placebo plus trastuzumab and chemotherapy for advanced HER2-positive gastric or gastro-oesophageal junction adenocarcinoma. In The Lancet Oncology, Sun Young Rha and colleagues2 published the final results of the KEYNOTE-859 trial, comparing first-line pembrolizumab plus chemotherapy with placebo plus chemotherapy for advanced HER2-negative gastric or gastro-oesophageal junction adenocarcinoma. Full-Text PDF