Sorroche Bruna Pereira, Teixeira Renan de Jesus, Pereira Caio Augusto Dantas, Santana Iara Viana Vidigal, Vujanovic Lazar, Vazquez Vinicius de Lima, Arantes Lidia Maria Rebolho Batista
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil.
Department of Clinical Oncology, Barretos Cancer Hospital, Barretos 14784-400, Brazil.
Diagnostics (Basel). 2023 Mar 9;13(6):1041. doi: 10.3390/diagnostics13061041.
Immune checkpoint blockade (ICB) agents are prominent immunotherapies for the treatment of advanced melanoma. However, they fail to promote any durable clinical benefit in a large cohort of patients. This study assessed clinical and molecular predictors of ICB response and survival in advanced melanoma. A retrospective analysis was performed on 210 patients treated with PD-1 or CTLA-4 inhibitors at Barretos Cancer Hospital, Brazil. PD-L1 expression was assessed by immunohistochemistry using formalin-fixed paraffin-embedded tumor tissues collected prior to ICB therapy. Patients were divided into responders (complete and partial response and stable disease for more than 6 months) and non-responders (stable disease for less than 6 months and progressive disease). Among them, about 82% underwent anti-PD-1 immunotherapy, and 60.5% progressed after the ICB treatment. Patients that received ICB as first-line therapy showed higher response rates than previously treated patients. Higher response rates were further associated with superficial spreading melanomas and positive PD-L1 expression (>1%). Likewise, PD-L1 positive expression and V600 mutations were associated with a higher overall survival after ICB therapy. Since ICBs are expensive therapies, evaluation of PD-L1 tumor expression in melanoma patients should be routinely assessed to select patients that are most likely to respond.
免疫检查点阻断(ICB)药物是治疗晚期黑色素瘤的重要免疫疗法。然而,它们未能在大量患者中带来任何持久的临床益处。本研究评估了晚期黑色素瘤患者ICB反应和生存的临床及分子预测指标。对巴西巴雷托斯癌症医院接受PD-1或CTLA-4抑制剂治疗的210例患者进行了回顾性分析。使用在ICB治疗前收集的福尔马林固定石蜡包埋肿瘤组织,通过免疫组织化学评估PD-L1表达。患者分为反应者(完全缓解、部分缓解和疾病稳定超过6个月)和无反应者(疾病稳定少于6个月和疾病进展)。其中,约82%接受了抗PD-1免疫治疗,60.5%在ICB治疗后病情进展。接受ICB作为一线治疗的患者显示出比先前治疗患者更高的反应率。更高的反应率还与浅表扩散性黑色素瘤和PD-L1阳性表达(>1%)相关。同样,PD-L1阳性表达和V600突变与ICB治疗后的总生存期延长相关。由于ICB治疗费用昂贵,应常规评估黑色素瘤患者的PD-L1肿瘤表达,以选择最可能有反应的患者。