Patrinely James R, Baker Laura X, Davis Elizabeth J, Song Haocan, Ye Fei, Johnson Douglas B
School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Cancer. 2020 Aug 1;126(15):3448-3455. doi: 10.1002/cncr.32984. Epub 2020 May 28.
Greater than one-half of patients with melanoma who are treated with antibodies blocking programmed cell death protein 1 receptor (anti-PD-1) experience disease progression. The objective of the current study was to identify prognostic factors and outcomes in patients with metastatic melanoma that progressed while they were receiving anti-PD-1 therapy.
The authors evaluated 383 consecutively treated patients who received anti-PD-1 for advanced melanoma between 2009 and 2019. Patient and disease characteristics at baseline and at the time of progression, subsequent therapies, objective response rate (ORR), overall survival, and progression-free survival were assessed.
Of 383 patients, 247 experienced disease progression. The median survival after progression was 6.8 months. There was no difference in survival noted after disease progression based on primary tumor subtype, receipt of prior therapy, or therapy type. However, significantly improved survival after disease progression correlated with clinical features at the time of progression, including normal lactate dehydrogenase, more favorable metastatic stage (American Joint Committee on Cancer eighth edition stage IV M1a vs M1b, M1c, or M1d), mutation status (NRAS or treatment-naive BRAF V600 vs BRAF/NRAS wild-type or treatment-experienced BRAF-mutant), decreasing tumor bulk, and progression at solely existing lesions. After progression, approximately 54.3% of patients received additional systemic therapy. A total of 41 patients received BRAF/MEK inhibition (ORR of 58.6%, including 70.4% for BRAF/MEK-naive patients), 30 patients received ipilimumab (ORR of 0%), and 11 patients received ipilimumab plus nivolumab (ORR of 27.3%).
The current study identified prognostic factors in advanced melanoma for patients who experienced disease progression while receiving anti-PD-1, including lactate dehydrogenase, stage of disease, site of disease progression, tumor size, and mutation status.
接受程序性细胞死亡蛋白1受体阻断抗体（抗PD-1）治疗的黑色素瘤患者中，超过一半会出现疾病进展。本研究的目的是确定在接受抗PD-1治疗期间出现进展的转移性黑色素瘤患者的预后因素和结局。
作者评估了2009年至2019年间连续接受抗PD-1治疗的383例晚期黑色素瘤患者。评估了基线和进展时的患者及疾病特征、后续治疗、客观缓解率（ORR）、总生存期和无进展生存期。
383例患者中，247例出现疾病进展。进展后的中位生存期为6.8个月。基于原发肿瘤亚型、既往治疗的接受情况或治疗类型，疾病进展后的生存期无差异。然而，疾病进展后生存期显著改善与进展时的临床特征相关，包括乳酸脱氢酶正常、更有利的转移分期（美国癌症联合委员会第八版IV期M1a与M1b、M1c或M1d）、突变状态（NRAS或初治BRAF V600与BRAF/NRAS野生型或经治BRAF突变型）、肿瘤体积减小以及仅在现有病灶处进展。进展后，约54.3%的患者接受了额外的全身治疗。共有41例患者接受BRAF/MEK抑制（ORR为58.6%，初治BRAF/MEK患者为70.4%），30例患者接受伊匹单抗（ORR为0%），11例患者接受伊匹单抗加纳武单抗（ORR为27.3%）。
本研究确定了接受抗PD-1治疗期间出现疾病进展的晚期黑色素瘤患者的预后因素，包括乳酸脱氢酶、疾病分期、疾病进展部位、肿瘤大小和突变状态。
