DISCUSSION
EVENTS
Results from the ESCC cohort of this Phase Ib study support a manageable safety profile of durvalumab with tremelimumab and chemotherapy for treatment of patients with advanced or metastatic ESCC. No unexpected safety events occurred that could be causally associated to study treatment by the investigators. In addition, most treatment‐related AEs that occurred were related to chemotherapy. The safety profile for durvalumab with tremelimumab and chemotherapy was generally consistent with other ICI studies in untreated advanced or metastatic ESCC, including KEYNOTE‐590 and CheckMate 648.Results from exploratory assessments in this study demonstrated antitumor activity with durvalumab in combination with tremelimumab and chemotherapy in patients with advanced or metastatic ESCC. In this study, the ORR was 37.5% and median DoR was 3.0 months. In addition, median OS and PFS were 9.7 and 3.8 months, respectively.The ORR and median OS reported in this study were generally comparable to prospective and retrospective studies of chemotherapy alone for the treatment of patients with advanced or metastatic ESCC, which have reported ORRs, ranging from 33.3% to 37.2%, and OS, ranging from 7 to 10 months.When compared with Phase III trials of ICIs combined with chemotherapy, including KEYNOTE‐590, CheckMate 648, and RATIONALE‐306, ORRs were generally lower, and median DoR, OS, and PFS were generally shorter in this study.Several reasons may explain the lower clinical response in this study compared with KEYNOTE‐590, CheckMate 648, and RATIONALE‐306, including the small number of patients enrolled in this study and the number of treatment cycles received.Limitations of the current study include the small number of patients enrolled in the ESCC cohort and the uncontrolled, single‐arm design. Overall, durvalumab with tremelimumab and chemotherapy demonstrated manageable safety and antitumor activity in patients with advanced or metastatic ESCC, warranting further investigation in randomized clinical trials.