PMID- 37489066 OWN - NLM STAT- MEDLINE DCOM- 20230901 LR - 20230902 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 12 IP - 15 DP - 2023 Aug TI - Safety and tolerability of first-line durvalumab with tremelimumab and chemotherapy in esophageal squamous cell carcinoma. PG - 16066-16075 LID - 10.1002/cam4.6260 [doi] AB - BACKGROUND: Advanced or metastatic esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis; new first-line systemic treatment options are needed. Combining immuno-oncology therapies with standard chemotherapy may represent a promising approach for the treatment of solid tumors. Results from a Phase Ib study evaluating durvalumab with tremelimumab and chemotherapy in patients with advanced or metastatic ESCC are reported. METHODS: Adults with advanced or metastatic ESCC who were candidates for first-line platinum-based chemotherapy received durvalumab 1500 mg (Day 1), tremelimumab 75 mg (Day 1), cisplatin 80 mg/m(2) (Day 1) and 5-fluorouracil (5-FU) 800 mg/m(2) (Days 1-5) in 28-day cycles until disease progression or discontinuation due to toxicity. The study consisted of safety run-in (Part A) and expansion (Part B) periods. The primary endpoint was safety. Antitumor activity was an exploratory endpoint. RESULTS: Sixteen patients were enrolled, 6 in Part A and 10 in Part B, and received a median of 4.0 treatment cycles. All patients were Asian; median age was 65.0 years. All patients experienced adverse events (AEs) related to cisplatin and 5-FU, and 8 (50.0%) patients experienced AEs related to durvalumab and tremelimumab. Grade >/=3 treatment-related AEs occurred in 7 (43.8%) patients. There were no deaths associated with AEs. Six (37.5%) patients achieved an objective response. Median progression-free survival was 3.75 months, and median overall survival was 9.69 months. CONCLUSIONS: Durvalumab with tremelimumab and chemotherapy demonstrated manageable safety and antitumor activity in patients with advanced or metastatic ESCC, warranting further investigation in randomized trials. Registered with ClinicalTrials.gov: NCT02658214. CI - (c) 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Lee, Dae Ho AU - Lee DH AD - Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. FAU - Kim, Hye Ryun AU - Kim HR AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. FAU - Keam, Bhumsuk AU - Keam B AUID- ORCID: 0000-0001-8196-4247 AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. FAU - Kato, Ken AU - Kato K AD - Department of Head and Neck, Esophageal Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Kuboki, Yasutoshi AU - Kuboki Y AD - Gastrointestinal Oncology Division, National Cancer Center Hospital, East Kashiwa, Japan. FAU - Gao, Haiyan AU - Gao H AD - AstraZeneca, Cambridge, UK. FAU - Yovine, Alejandro AU - Yovine A AD - AstraZeneca, Cambridge, UK. FAU - Robbins, Scott H AU - Robbins SH AD - AstraZeneca, Gaithersburg, Maryland, USA. FAU - Ahn, Myung-Ju AU - Ahn MJ AUID- ORCID: 0000-0002-5740-9654 AD - Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea. LA - eng SI - ClinicalTrials.gov/NCT02658214 PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230725 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 28X28X9OKV (durvalumab) RN - QEN1X95CIX (tremelimumab) RN - Q20Q21Q62J (Cisplatin) RN - U3P01618RT (Fluorouracil) SB - IM MH - Adult MH - Humans MH - Aged MH - *Esophageal Squamous Cell Carcinoma/drug therapy/etiology MH - Cisplatin/adverse effects MH - *Esophageal Neoplasms/drug therapy/etiology MH - Fluorouracil/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects PMC - PMC10469840 OTO - NOTNLM OT - chemotherapy OT - clinical trials OT - esophageal squamous cell OT - immunology COIS- Dae Ho Lee: Personal fees: AbbVie, AstraZeneca, BC Pharma, Boehringer Ingelheim, Bristol-Myers Squibb, ChongKeunDang, CJ Healthcare, Eli Lilly, Genexine, Janssen, Menarini, Merck, MSD, Mundipharma, Novartis, ONO, Pfizer, Roche, Samyang Biopharm, ST Cube, Takeda. Non-financial support: Blueprint Medicines, Takeda. Hye Ryun Kim: Consultant/advisor: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Takeda. Honoraria: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, ONO. Research funding: AstraZeneca, Bristol-Myers Squibb, ONO, YUHAN. Bhumsuk Keam: Research funding: AstraZeneca, MSD Oncology, ONO. Consultant/advisor: ABL Bio, AstraZeneca, CbsBioscience, Cellid, Genexine, Handok, MSD Oncology. Honoraria: AstraZeneca, Merck, MSD Oncology. Ken Kato: Research funding: AstraZeneca, Bayer, BeiGene, Chugai, Merck, Merck Serono, MSD, Oncolys BioPharma, ONO, Shionogi. Yasutoshi Kuboki: Research funding: Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Genmab, GSK, Incyte, Lilly, ONO, Taiho, Takeda. Honoraria: Bayer, Bristol-Myers Squibb, Lilly, Merck Serono, ONO, Taiho. Haiyan Gao, Alejandro Yovine, and Scott H. Robbins: Employees/shareholders: AstraZeneca. Myung-Ju Ahn: Consultant/advisor: Alpha Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, MSD, Novartis, Roche, Takeda. Honoraria: AstraZeneca, Bristol-Myers Squibb, MSD, ONO, Roche. EDAT- 2023/07/25 06:42 MHDA- 2023/09/01 06:43 PMCR- 2023/07/25 CRDT- 2023/07/25 03:14 PHST- 2023/06/05 00:00 [revised] PHST- 2022/05/04 00:00 [received] PHST- 2023/06/05 00:00 [accepted] PHST- 2023/09/01 06:43 [medline] PHST- 2023/07/25 06:42 [pubmed] PHST- 2023/07/25 03:14 [entrez] PHST- 2023/07/25 00:00 [pmc-release] AID - CAM46260 [pii] AID - 10.1002/cam4.6260 [doi] PST - ppublish SO - Cancer Med. 2023 Aug;12(15):16066-16075. doi: 10.1002/cam4.6260. Epub 2023 Jul 25.