Encouraging results for PD-1 inhibition in gastric cancer

Abstract

The prognosis for advanced gastric cancer is poor: less than 10–15% of patients with metastases live for more than 2 years. Trastuzumab and ramucirumab have resulted in modest improvements in overall survival for patients with HER2-positive gastric cancer and in the second-line setting, respectively. 1 Bang YJ Van Cutsem E Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376: 687-697 Google Scholar , 2 Wilke H Muro K Van Cutsem E et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014; 15: 1224-1235 Google Scholar However, these drugs are notable for their success in a field in which there have been many failures. 1 Bang YJ Van Cutsem E Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376: 687-697 Google Scholar , 2 Wilke H Muro K Van Cutsem E et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014; 15: 1224-1235 Google Scholar , 3 Ohtsu A Shah MA Van Cutsem E et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011; 29: 3968-3976 Google Scholar , 4 Waddell T Chau I Cunningham D et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013; 14: 481-489 Google Scholar Within this challenging therapeutic context, the results of the KEYNOTE-012 study by Kei Muro and colleagues 5 Muro K Chung HC Shankaran V et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016; (published online May 3.)http://dx.doi.org/10.1016/S1470-2045(16)00175-3 Google Scholar are promising. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trialIn this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials. Full-Text PDF