Response to Letter to the Editor: Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: A Randomized, Double-Blind, Phase 3 Study (ORIENT-11)

Thank you for the comments. Pembrolizumab was approved in combination with pemetrexed and platinum by the U.S. Food and Drug Administration as first-line therapy in patients with advanced nonsquamous NSCLC on August 20, 2018, and this indication was approved by the National Medical Products Administration (NMPA) of the People’s Republic of China on March 28, 2019. Therefore, when the ORIENT-11 study was initiated in August 2018, pembrolizumab had not yet been approved in the People’s Republic of China. There remained great unmet medical needs in Chinese patients before the approval of pembrolizumab. Thus, the ORIENT-11 study was in accordance with ethical standards under such circumstances. Furthermore, the KEYNOTE-189 study was conducted mainly among whites, with only 1.6% enrollment of East Asian patients.1Gandhi L. Rodríguez-Abreu D. Gadgeel S. et al.Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer.N Engl J Med. 2018; 378: 2078-2092Crossref PubMed Scopus (2341) Google Scholar Thus, even after the approval of pembrolizumab for this indication in the People’s Republic of China, exploring this combination regimen in the Chinese patient population is still of great importance. Regarding the primary end point, progression-free survival is accepted as a surrogate end point in phase 3 NSCLC studies for registration by both the U.S. Food and Drug Administration2U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER)Clinical trial endpoints for the approval of non-small cell lung cancer drugs and biologics guidance for industry.https://www.fda.gov/media/116860/downloadGoogle Scholar,3U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER)Multiple endpoints in clinical trials guidance for industry draft guidance.https://www.fda.gov/media/102657/downloadGoogle Scholar and NMPA.4China Food and Drug International Exchange CenterThe centers for drug evaluation publicly solicits opinions on the “guidance for the statistical design of antitumor drug clinical trials.”.http://www.ccfdie.org/cn/yjxx/yphzp/webinfo/2020/07/1592160852573198.htmGoogle Scholar As it was a registration study, the study design of ORIENT-11 was communicated to NMPA and received acceptance before the study initiation. In addition, overall survival was the key secondary end point of this study. The preliminary result of our study revealed that sintilimab combined with pemetrexed and platinum could reduce the risk of death compared with pemetrexed and platinum alone. We will continue to follow up to obtain data on overall survival and report the results in the near future. Comparing Immunotherapies in Combination With Chemotherapy for Previously Untreated Advanced Nonsquamous NSCLCJournal of Thoracic OncologyVol. 15Issue 12PreviewWe read with great interest the work of Yang et al.1 (ORIENT-11) comparing sintilimab, an anti–programmed cell death protein 1 (PD-1) antibody, in combination with chemotherapy, and appreciate their contributions to the treatment of advanced nonsquamous NSCLC in Asia. In fact, the U.S. Food and Drug Administration approved this indication on the basis of a very similar phase 3 study (KEYNOTE-189) around 2 years ago.2 We performed an adjusted indirect comparison between the results of ORIENT-11 and updated KEYNOTE-1893 using the methods described previously. Full-Text PDF