Abstract:
The treatment landscape for advanced and metastatic melanoma has drastically changed in recent years, with the advent of novel therapeutic options such as immune checkpoint inhibitors and targeted therapies offering remarkable efficacy and significantly improved patient outcomes compared to traditional approaches. Approximately 50% of melanomas harbor activating BRAF mutations, with over 90% resulting in BRAF V600E. Tumors treated with BRAF inhibitor monotherapy have a high rate of developing resistance within six months. Combination therapy with MEK inhibitors helped to mitigate this treatment resistance and led to improved outcomes. Due to the up-regulation of PD-1/PD-L1 receptors in tumors treated with BRAF/MEK inhibitor therapy, further studies included a third combination agent, anti-PD-1/PD-L1 inhibitors. This triple combination therapy may have superior efficacy and a manageable safety profile when compared with single or double agent therapy regimens.
Effective treatment of advanced and metastatic melanoma can be challenging. Newer treatment methods for patients with BRAF-mutated tumors include a combination of drugs with different complementary mechanisms. These drugs include BRAF-inhibitors, MEK-inhibitors, and PD-1/PD-L1 inhibitors. When these three medications are used in combination, patients may have better response rates and survival outcomes, when compared to using just one or two of these medications together. Toxicity rates are higher with a triple-medication regimen, so careful patient selection is important to consider.
摘要:
近年来,晚期和转移性黑色素瘤的治疗前景发生了巨大变化,随着免疫检查点抑制剂和靶向治疗等新型治疗方案的出现,与传统方法相比,该方法具有显着疗效并显着改善了患者预后。大约50%的黑色素瘤有激活的BRAF突变,超过90%导致BRAFV600E。用BRAF抑制剂单一疗法治疗的肿瘤在6个月内具有高的发展耐药率。与MEK抑制剂的联合治疗有助于减轻这种治疗耐药性并导致改善的结果。由于在BRAF/MEK抑制剂治疗的肿瘤中PD-1/PD-L1受体的上调,进一步的研究包括第三种联合药物,抗PD-1/PD-L1抑制剂。与单剂或双剂治疗方案相比,这种三联联合治疗可能具有更好的疗效和可控的安全性。
晚期和转移性黑色素瘤的有效治疗可能具有挑战性。BRAF突变肿瘤患者的较新治疗方法包括具有不同互补机制的药物组合。这些药物包括BRAF抑制剂,MEK抑制剂,和PD-1/PD-L1抑制剂。当这三种药物联合使用时,患者可能有更好的反应率和生存结果,与一起使用这些药物中的一种或两种相比。三联用药方案的毒性更高,所以仔细选择病人是很重要的。