PMID- 37741071 OWN - NLM STAT- Publisher LR - 20231015 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 193 DP - 2023 Nov TI - A phase II study on the efficacy of regorafenib in treating patients with c-KIT-mutated metastatic malignant melanoma that progressed after previous treatment (KCSG-UN-14-13). PG - 113312 LID - S0959-8049(23)00414-8 [pii] LID - 10.1016/j.ejca.2023.113312 [doi] AB - BACKGROUND: c-KIT mutations are found in approximately 15% of patients with malignant melanoma in the Asian population. Regorafenib, an oral multikinase inhibitor, acts against both wild-type and mutant KIT. OBJECTIVE: This multi-institutional, phase II, single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harbouring c-KIT mutations. METHODS: Patients with metastatic melanoma positive for c-KIT mutations, upon progression after at least one line of systemic treatment, were enroled. Patients received oral regorafenib 160 mg once daily for 3 weeks (4-week cycle). The primary endpoint was disease control rate (DCR), and secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 23 patients were enrolled. c-KIT mutations were frequently reported in exon 11 (14/23, 60.9%), followed by exons 13, 17, and 9 in 5 (21.7%), 5 (21.7%), and 2 (8.7%) patients, respectively. DCR at 8 weeks was 73.9%, with 2 patients (8.7%) achieving complete response, 5 (21.7%) achieving partial response, and 10 (43.5%) showing stable disease. ORR was 30.4% (7/23). The median follow-up period was 15.7 months (95% confidence interval [CI], 9.6-21.3), and median OS and PFS were 21.5 months (95% CI, 15.1-27.9) and 7.1 months (95% CI, 5.0-9.2), respectively. Circulating tumour DNA analysis in selected patients showed high c-KIT correlation (85.7%) with tissue-based tumour mutational profiles. The most common adverse events (AEs) were skin reactions, including palmar-plantar erythrodysesthesia (52.2%), and grade 3 AEs were reported in 39.1% (9/23) of the patients. CONCLUSION: Regorafenib in second- or later-line settings demonstrated significant activity in patients with metastatic melanoma harbouring c-KIT mutations. CI - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Kim, Kyoo Hyun AU - Kim KH AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Jung, Minkyu AU - Jung M AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Lee, Hyo Jin AU - Lee HJ AD - Department of Internal Medicine and Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea. FAU - Lee, Su Jin AU - Lee SJ AD - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Divison of Hematology-Oncology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Republic of Korea. FAU - Kim, Miso AU - Kim M AD - Department of Internal Medicine, Seoul National University Hospital, Seoul National University Cancer Research Institute, Seoul, Republic of Korea. FAU - Ahn, Mi Sun AU - Ahn MS AD - Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Republic of Korea. FAU - Choi, Moon Young AU - Choi MY AD - Department of Internal Medicine, Hemato-Oncology, Inje University Busan Paik Hospital, Busan, Republic of Korea. FAU - Lee, Na-Ri AU - Lee NR AD - Division of Hematology and Oncology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea. FAU - Shin, Sang Joon AU - Shin SJ AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: ssj338@yuhs.ac. CN - Korean Cancer Study Group (KCSG) LA - eng PT - Journal Article DEP - 20230828 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 SB - IM OTO - NOTNLM OT - C-KIT mutation OT - Circulating tumour DNA OT - Malignant melanoma OT - Regorafenib COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/09/24 00:42 MHDA- 2023/09/24 00:42 CRDT- 2023/09/23 18:04 PHST- 2023/06/29 00:00 [received] PHST- 2023/08/14 00:00 [revised] PHST- 2023/08/22 00:00 [accepted] PHST- 2023/09/24 00:42 [pubmed] PHST- 2023/09/24 00:42 [medline] PHST- 2023/09/23 18:04 [entrez] AID - S0959-8049(23)00414-8 [pii] AID - 10.1016/j.ejca.2023.113312 [doi] PST - ppublish SO - Eur J Cancer. 2023 Nov;193:113312. doi: 10.1016/j.ejca.2023.113312. Epub 2023 Aug 28.