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REVIEW article

Front. Pharmacol.
Sec. Drugs Outcomes Research and Policies
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1457226

Cutaneous Adverse Events Associated With BRAF and MEK Inhibitors: A Systematic Review and Meta-analysis

Provisionally accepted
Junhui Qian Junhui Qian 1*Jinlong Wan Jinlong Wan 2Qin Yao Qin Yao 1*Yin Chen Yin Chen 3*Tao Ling Tao Ling 3,4*Yuejuan Zhang Yuejuan Zhang 1*Zhihua Tang Zhihua Tang 1*
  • 1 Department of Pharmacy, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China
  • 2 Department of Gastroenterology, The People’s Hospital of Gaozhou, Gaozhou, China
  • 3 Department of Pharmacy, Suqian First Hospital, Suqian, Jiangsu Province, China
  • 4 Suqian First Hospital, China, China

The final, formatted version of the article will be published soon.

    ： Aim: Cutaneous adverse events (CAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. To determine the association of BRAF and MEK inhibitor treatment with CAEs in patients with melanoma compared with BRAF inhibitor alone. Method: PubMed, Cochrane, Embase and Web of Science were systematically searched for BRAF and MEK inhibitors from database inception through May 10, 2024. Randomized clinical trials reporting on CAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected. Pooled relative risks (RRs) and 95% CIs were determined using random-effects analyses. The selected end points were alopecia, cutaneous squamous-cell carcinoma, hyperkeratosis, keratoacanthoma, palmoplantar erythrodysaesthesia syndrome, palmoplantar keratoderma, rash, photosensitivity reaction, and skin papilloma. All-grade and high-grade (≥3) CAEs were recorded.Comparing with BRAF and MEK inhibitors, treatment with BRAF inhibitors alone was associated with an increased risk of rash (RR, 0.73; 95% CI, 0.54-0.99; P=0.039; I 2 = 88%), alopecia (RR, 0.28; 95% CI, 0.20-0.41; P ＜ 0.001; I 2 = 76%), hyperkeratosis (RR, 0.30; 95% CI, 0.22-0.41; P ＜ 0.001; I 2 = 56%), palmoplantar erythrodysaesthesia syndrome (RR, 0.21; 95% CI, 0.10-0.47; P ＜ 0.001; I 2 = 81%), palmoplantar keratoderma (RR, 0.39; 95% CI, 0.26-0.57; P＜0.001; I 2 = 29%), Skin papilloma(RR, 0.25; 95% CI, 0.12-0.52; P ＜ 0.001; I 2 = 77%), cutaneous squamous-cell carcinoma (RR, 0.21; 95% CI, 0.11-0.42; P ＜ 0.001; I 2 = 50%), and keratoacanthoma (RR, 0.22; 95% CI, 0.12-0.40; P ＜ 0.001; I 2 = 0%). Conclusions:Therapy with BRAF and MEK inhibitors was associated with a lower risk of CAEs, especially rash, alopecia, hyperkeratosis, palmoplantar erythrodysaesthesia syndrome, palmoplantar keratoderma, skin papilloma, cutaneous squamous-cell carcinoma, and keratoacanthoma, compared with BRAF inhibitor alone. The risks of photosensitivity reaction was similar between the assessed groups. The findings may help to balance between beneficial melanoma treatment and cutaneous morbidity and mortality.

    Keywords: cutaneous adverse events, BRAF inhibitor, mek inhibitor, Melanoma, meta analysis

    Received: 09 Aug 2024; Accepted: 26 Nov 2024.

    Copyright: © 2024 Qian, Wan, Yao, Chen, Ling, Zhang and Tang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Junhui Qian, Department of Pharmacy, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China
    Qin Yao, Department of Pharmacy, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China
    Yin Chen, Department of Pharmacy, Suqian First Hospital, Suqian, Jiangsu Province, China
    Tao Ling, Suqian First Hospital, China, China
    Yuejuan Zhang, Department of Pharmacy, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China
    Zhihua Tang, Department of Pharmacy, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.