{"title":"与BRAF和MEK抑制剂相关的皮肤不良事件：系统回顾和荟萃分析。","authors":"Junhui Qian, Jinlong Wan, Qin Yao, Yin Chen, Tao Ling, Yuejuan Zhang, Zhihua Tang","doi":"10.3389/fphar.2024.1457226","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Method: </strong>PubMed, Cochrane, Embase and Web of Science were systematically searched for BRAF and MEK inhibitors from database inception through 10 May 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 Risk ratios (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.</p><p><strong>Results: </strong>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; <i>p</i> = 0.039; I<sup>2</sup> = 88%), alopecia (RR, 0.28; 95% CI, 0.20-0.41; P < 0.001; I<sup>2</sup> = 76%), hyperkeratosis (RR, 0.30; 95% CI, 0.22-0.41; P < 0.001; I<sup>2</sup> = 56%), palmoplantar erythrodysaesthesia syndrome (RR, 0.21; 95% CI, 0.10-0.47; P < 0.001; I<sup>2</sup> = 81%), palmoplantar keratoderma (RR, 0.39; 95% CI, 0.26-0.57; P < 0.001; I<sup>2</sup> = 29%), Skin papilloma (RR, 0.25; 95% CI, 0.12-0.52; P < 0.001; I<sup>2</sup> = 77%), cutaneous squamous-cell carcinoma (RR, 0.21; 95% CI, 0.11-0.42; P < 0.001; I<sup>2</sup> = 50%), and keratoacanthoma (RR, 0.22; 95% CI, 0.12-0.40; P < 0.001; I<sup>2</sup> = 0%).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1457226"},"PeriodicalIF":4.4000,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703664/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cutaneous adverse events associated with BRAF and MEK inhibitors: a systematic review and meta-analysis.\",\"authors\":\"Junhui Qian, Jinlong Wan, Qin Yao, Yin Chen, Tao Ling, Yuejuan Zhang, Zhihua Tang\",\"doi\":\"10.3389/fphar.2024.1457226\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>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.</p><p><strong>Method: </strong>PubMed, Cochrane, Embase and Web of Science were systematically searched for BRAF and MEK inhibitors from database inception through 10 May 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 Risk ratios (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.</p><p><strong>Results: </strong>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; <i>p</i> = 0.039; I<sup>2</sup> = 88%), alopecia (RR, 0.28; 95% CI, 0.20-0.41; P < 0.001; I<sup>2</sup> = 76%), hyperkeratosis (RR, 0.30; 95% CI, 0.22-0.41; P < 0.001; I<sup>2</sup> = 56%), palmoplantar erythrodysaesthesia syndrome (RR, 0.21; 95% CI, 0.10-0.47; P < 0.001; I<sup>2</sup> = 81%), palmoplantar keratoderma (RR, 0.39; 95% CI, 0.26-0.57; P < 0.001; I<sup>2</sup> = 29%), Skin papilloma (RR, 0.25; 95% CI, 0.12-0.52; P < 0.001; I<sup>2</sup> = 77%), cutaneous squamous-cell carcinoma (RR, 0.21; 95% CI, 0.11-0.42; P < 0.001; I<sup>2</sup> = 50%), and keratoacanthoma (RR, 0.22; 95% CI, 0.12-0.40; P < 0.001; I<sup>2</sup> = 0%).</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":12491,\"journal\":{\"name\":\"Frontiers in Pharmacology\",\"volume\":\"15 \",\"pages\":\"1457226\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-12-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703664/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fphar.2024.1457226\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fphar.2024.1457226","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Cutaneous adverse events associated with BRAF and MEK inhibitors: a systematic review and meta-analysis.
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 10 May 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 Risk ratios (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.
Results: 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; I2 = 88%), alopecia (RR, 0.28; 95% CI, 0.20-0.41; P < 0.001; I2 = 76%), hyperkeratosis (RR, 0.30; 95% CI, 0.22-0.41; P < 0.001; I2 = 56%), palmoplantar erythrodysaesthesia syndrome (RR, 0.21; 95% CI, 0.10-0.47; P < 0.001; I2 = 81%), palmoplantar keratoderma (RR, 0.39; 95% CI, 0.26-0.57; P < 0.001; I2 = 29%), Skin papilloma (RR, 0.25; 95% CI, 0.12-0.52; P < 0.001; I2 = 77%), cutaneous squamous-cell carcinoma (RR, 0.21; 95% CI, 0.11-0.42; P < 0.001; I2 = 50%), and keratoacanthoma (RR, 0.22; 95% CI, 0.12-0.40; P < 0.001; I2 = 0%).
Conclusion: 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.
期刊介绍：
Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
