Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea.
Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Precision Medicine Research Institute, Samsung Medical Center, Seoul, Korea.
ESMO Open. 2021 Feb;6(1):100002. doi: 10.1016/j.esmoop.2020.100002. Epub 2020 Dec 16.
Melanoma is major medical challenge and being able to monitor treatment response is critical. This study aimed to use molecular profiling of Asian patients with advanced melanoma who were receiving treatment with check-point inhibitors (CPIs) to identify novel biomarkers of tumor response.
Next-generation sequencing (NGS) was performed using tumor specimens collected from 178 Asian patients with metastatic melanoma receiving CPIs. The NGS data and clinical-pathological factors were analyzed for potential genetic biomarkers of tumor response to CPI treatment.
The most common melanoma subtype was acral melanoma (40%), followed by cutaneous melanoma (32%), mucosal melanoma (26%), and others (2%). For calculation of treatment efficacy, 164 of the patients could be evaluated. The overall response rate was 45.7%, of which 41 cases exhibited complete responses (25.0%) and 34 showed partial responses (20.7%). There were no significant differences in tumor responses based on melanoma subtype (P = 0.295). Genetically, NRAS mutations, TP53 mutations, and NF2 deletions were significantly associated with resistance to CPIs (P < 0.05). In contrast, MYC and RPS6KB1 amplifications were associated with responsiveness to CPIs (P < 0.05). Median progression-free survival (PFS) for patients treated with CPIs was 5.9 months (95% CI, 3.8-8.05 months). Univariate analysis identified TP53 and BRAF mutations, NF2 deletions, and BIRC2 amplifications as poor prognostic factors for PFS (P < 0.05).
This study determined the integrated genomic profiles of Asian patients with metastatic melanoma receiving CPIs and identified candidate biomarkers that reflected treatment outcomes.
黑色素瘤是一项重大的医学挑战，能够监测治疗反应至关重要。本研究旨在通过对接受检查点抑制剂（CPIs）治疗的亚洲晚期黑色素瘤患者进行分子谱分析，确定肿瘤反应的新型生物标志物。
对 178 名接受 CPIs 治疗的转移性黑色素瘤亚洲患者的肿瘤标本进行下一代测序（NGS）。分析 NGS 数据和临床病理因素，以确定 CPI 治疗肿瘤反应的潜在遗传生物标志物。
最常见的黑色素瘤亚型为肢端黑色素瘤（40%），其次为皮肤黑色素瘤（32%）、黏膜黑色素瘤（26%）和其他类型（2%）。为了计算治疗效果，可对 164 名患者进行评估。总体缓解率为 45.7%，其中完全缓解 41 例（25.0%），部分缓解 34 例（20.7%）。不同黑色素瘤亚型的肿瘤反应无显著差异（P=0.295）。从基因角度看，NRAS 突变、TP53 突变和 NF2 缺失与 CPIs 耐药显著相关（P<0.05）。相反，MYC 和 RPS6KB1 扩增与 CPIs 敏感性相关（P<0.05）。CPIs 治疗患者的中位无进展生存期（PFS）为 5.9 个月（95%CI，3.8-8.05 个月）。单因素分析确定 TP53 和 BRAF 突变、NF2 缺失和 BIRC2 扩增是 PFS 的不良预后因素（P<0.05）。
本研究确定了接受 CPIs 治疗的亚洲转移性黑色素瘤患者的综合基因组谱，并确定了反映治疗结果的候选生物标志物。
