MEDI0457 Plus Durvalumab in HPV-associated HNSCC—Letter

We read with interest the article by Aggarwal and colleagues (1). The authors should be congratulated on the well-designed phase Ib/IIa trial to investigate the safety and efficacy of the combination treatment of MEDI0457 and durvalumab in human papillomavirus–associated recurrent/metastatic head and neck squamous cell carcinoma. They concluded that MEDI0457 plus durvalumab was well tolerated, but the primary efficacy endpoint was not reached. We think that the authors can say that primary efficacy was met because of the reason described below.As the primary endpoint, the objective response rate (ORR) was evaluated. The authors planned to test the null hypothesis that the ORR was less than or equal to 15% with a one-sided significance level of 10%. In terms of a confidence interval (CI), the null hypothesis is rejected if the lower limit of the two-sided CI for ORR with the confidence coefficient of 80% is more than 15%.In the result of the trial, the ORR was 27.6% (8/29), 80% CI was 16.8% to 40.9% calculated by the Clopper–Pearson method, and the lower limit was more than 15%. Then the null hypothesis can be rejected and the authors could say that the primary endpoint is met.Of course, it is important to output 95% CIs for comparison with other studies, such as systematic reviews that include nonrandomized studies. For this purpose, the 95% CI and the 80% CI or lower limit that have already been output may be written together.See the Response, p. 2736K. Mori reports personal fees from Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Dankyo Co., Ltd., and Eli Lilly Japan K.K. outside the submitted work. K. Miura reports personal fees from Chugai Pharmaceutical and Taiho Pharmaceutical outside the submitted work. No disclosures were reported by the other authors.