Outcome of combination therapy using BRAF and MEK inhibitors among Asian patients with advanced melanoma: An analysis of 112 cases.

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.

• Authors: Yasuhiro Fujisawa, Takamichi Ito, Hiroshi Kato, Hiroyuki Irie, Tatsuya Kaji, Takeo Maekawa, Jun Asai, Yuki Yamamoto, Taku Fujimura, Yasuo Nakai, Masahito Yasuda, Kanako Matsuyama, Ikko Muto, Shigeto Matsushita, Hiroshi Uchi, Yoshiyuki Nakamura, Jiro Uehara, Koji Yoshino
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 145 Pg. 210-220 (03 2021) ISSN: 1879-0852 [Electronic] England
• PMID: 33503528 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Protein Kinase Inhibitors
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Mitogen-Activated Protein Kinase Kinases

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Asian People
• Female
• Humans
• Japan (epidemiology)
• Male
• Melanoma (drug therapy, enzymology, ethnology, mortality)
• Middle Aged
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, metabolism)
• Progression-Free Survival
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Proto-Oncogene Proteins B-raf (antagonists & inhibitors, metabolism)
• Retrospective Studies
• Skin Neoplasms (drug therapy, enzymology, ethnology, mortality)
• Time Factors
• Young Adult