Mackiewicz Jacek, Mackiewicz Andrzej
Department of Medical and Experimental Oncology, Heliodor Swiecicki University Hospital, Poznan University of Medical Sciences, Poland.
Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
Contemp Oncol (Pozn). 2018 Mar;22(1A):68-72. doi: 10.5114/wo.2018.73890. Epub 2018 Mar 5.
The treatment landscape in advanced melanoma is changing dramatically with the approval of new drugs. Vemurafenib was the first approved targeted agent for the treatment of -mutant advanced melanoma. However, treatment with a BRAF inhibitor is linked with acquired resistance occurring in half of the patients after approximately six months. Combination of MEK and BRAF inhibitor therapy results in extension of the time to resistance, translating into longer overall survival of treated patients. Similar clinical benefits are observed with therapy using antibodies against immune-checkpoint inhibitors in the same patient population. Due to the fact that results of randomised studies comparing these two treatment strategies back to back have not been presented yet, the best first and second line treatment option in patients with -mutant melanoma is unknown. Currently, phase 3 studies are also evaluating the efficacy of targeted therapy combined with immunotherapy in patients with -mutant and wild-type advanced melanoma. Identifying a biomarker for the selection of patients benefiting most from the treatment will be crucial for further survival improvement in patients with advanced melanoma.
随着新药的获批，晚期黑色素瘤的治疗格局正在发生巨大变化。维莫非尼是首个获批用于治疗BRAF突变型晚期黑色素瘤的靶向药物。然而，使用BRAF抑制剂治疗与大约六个月后半数患者出现获得性耐药有关。MEK和BRAF抑制剂联合治疗可延长耐药时间，从而使接受治疗的患者总生存期延长。在同一患者群体中，使用抗免疫检查点抑制剂抗体治疗也观察到了类似的临床益处。由于尚未公布直接比较这两种治疗策略的随机研究结果，BRAF突变型黑色素瘤患者的最佳一线和二线治疗方案尚不清楚。目前，3期研究也在评估靶向治疗联合免疫治疗对BRAF突变型和野生型晚期黑色素瘤患者的疗效。识别能够选择出从治疗中获益最大的患者的生物标志物，对于进一步提高晚期黑色素瘤患者的生存率至关重要。
