Yasuhiro Fujisawa1, Takamichi Ito2, Hiroshi Kato3, Hiroyuki Irie4, Tatsuya Kaji5, Takeo Maekawa6, Jun Asai7, Yuki Yamamoto8, Taku Fujimura9, Yasuo Nakai10, Masahito Yasuda11, Kanako Matsuyama12, Ikko Muto13, Shigeto Matsushita14, Hiroshi Uchi15, Yoshiyuki Nakamura16, Jiro Uehara17, Koji Yoshino17. 1. Department of Dermatology, University of Tsukuba, Japan. Electronic address: fujisan@md.tsukuba.ac.jp. 2. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Japan. 3. Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Japan. 4. Department of Dermatology, Kyoto University Graduate School of Medicine, Japan. 5. Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan. 6. Department of Dermatology, Jichi Medical University, Japan. 7. Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan. 8. Department of Dermatology, Wakayama Medical University, Japan. 9. Department of Dermatology,Tohoku University Graduate School of Medicine, Japan. 10. Department of Dermatology, Mie University Graduate School of Medicine, Tsu, Mie, Japan. 11. Department of Dermatology, University of Gunma, Japan. 12. Department of Dermatology, University of Gifu, Japan. 13. Department of Dermatology, Kurume University School of Medicine, Japan. 14. Department of Dermato-Oncology / Dermatology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan. 15. Department Dermato-Oncology, National Hospital Organization Kyushu Cancer Center, Japan. 16. Department of Dermatology, University of Tsukuba, Japan. 17. Department of Dermatologic Oncology, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Japan.
Abstract
BACKGROUND: As most clinical trials evaluating BRAF and MEK inhibitor combination therapy (B + Minh) have been conducted in Western countries, little is known about the effect of B + Minh among East Asian populations. MATERIAL AND METHODS: Data from patients with advanced melanoma treated using B + Minh (either dabrafenib + trametinib or encorafenib + binimetinib) were retrospectively collected from 16 institutes in Japan. Response rates, adverse events, patterns of failure and survival were analysed. RESULTS: We analysed 112 of 144 collected patient records and, of these, 14 had acral/mucosal melanoma. The response rate for the entire cohort was 75.0%. There were no statistical differences in response rates between acral/mucosal and cutaneous melanomas (64.3% versus 76.5%), whereas previous treatment using immune checkpoint inhibitors (ICIs) did not affect response (72.7% versus 73.9%) to B + Minh, response to ICI after B + Minh was only 20%. Patients who achieved complete response had the best overall survival rates at 24 months (94.7%). Elevated serum lactate dehydrogenase levels and 3 or more metastatic sites were independently associated with survival. The most common relapse site was the brain (17.9%). More than half of the patients (58.8%) experienced grade III/IV pyrexia. CONCLUSION: B + Minh was effective among Japanese patients with melanoma, including those with acral/mucosal melanoma. Factors associated with survival were similar to previous Western studies. B + Minh response was not affected by the previous use of ICI; however, vigilance against brain metastasis during B + Minh therapy is required as the brain was our most commonly encountered relapse site.
BACKGROUND: As most clinical trials evaluating BRAF and MEK inhibitor combination therapy (B + Minh) have been conducted in Western countries, little is known about the effect of B + Minh among East Asian populations. MATERIAL AND METHODS: Data from patients with advanced melanoma treated using B + Minh (either dabrafenib + trametinib or encorafenib + binimetinib) were retrospectively collected from 16 institutes in Japan. Response rates, adverse events, patterns of failure and survival were analysed. RESULTS: We analysed 112 of 144 collected patient records and, of these, 14 had acral/mucosal melanoma. The response rate for the entire cohort was 75.0%. There were no statistical differences in response rates between acral/mucosal and cutaneous melanomas (64.3% versus 76.5%), whereas previous treatment using immune checkpoint inhibitors (ICIs) did not affect response (72.7% versus 73.9%) to B + Minh, response to ICI after B + Minh was only 20%. Patients who achieved complete response had the best overall survival rates at 24 months (94.7%). Elevated serum lactate dehydrogenase levels and 3 or more metastatic sites were independently associated with survival. The most common relapse site was the brain (17.9%). More than half of the patients (58.8%) experienced grade III/IV pyrexia. CONCLUSION: B + Minh was effective among Japanese patients with melanoma, including those with acral/mucosal melanoma. Factors associated with survival were similar to previous Western studies. B + Minh response was not affected by the previous use of ICI; however, vigilance against brain metastasis during B + Minh therapy is required as the brain was our most commonly encountered relapse site.