Department of General and Oncologic Dermatology, Ambroise-Paré Hospital, APHP & EA 4340 Biomarkers in Cancerology and Hemato-Oncology, UVSQ, Université Paris-Saclay, Paris, France.
Department of Public Health, Ambroise-Paré Hospital, APHP & UVSQ, Université Paris-Saclay, Paris, France.
Int J Cancer. 2020 Sep 15;147(6):1707-1714. doi: 10.1002/ijc.32934. Epub 2020 Feb 28.
Advanced melanoma patients who failed anti-PD-1 therapy have limited options. We analyzed a cohort of 133 advanced melanoma patients receiving anti-PD-1 monotherapy in a referral center between April 2015 and December 2017, and included the 26 patients with confirmed progressive (PD) or stable disease who received additional radiotherapy with an unmodified anti-PD-1 mAb regimen. Tumor evaluations were done on radiated and nonradiated (RECIST 1.1) lesions, with abscopal effect defined as a partial (PR) or complete response (CR) outside radiated fields. Primary endpoint was the CR + PR rate in radiated + nonradiated lesions. Secondary endpoints were progression-free survival (PFS), melanoma-specific survival (MSS) and safety. First late radiotherapy, consisting of hypofractionated radiotherapy (3-5 sessions, 20-26 Gy), standard palliative radiotherapy or brain radiosurgery was begun after a median of 6.3 months of anti-PD-1 in 23, 2 and 1 patient(s), respectively. Best response was 8 (31%) CR, 2 (8%) profound PR allowing surgical resection of remaining metastases and 16 (62%) PD. Abscopal effect was seen in 35% of patients. Median PFS and MSS since anti-PD-1 initiation was 15.2 [95% CI: 8.0 not achieved (na)] and 35.3 [95% CI: 18.5 na] months, respectively. PFS curves seemed to achieve a plateau. We discontinued anti-PD-1 therapy in 9/10 of patients with no residual evaluable disease and observed one relapse after a median of 10 months off anti-PD1-therapy. No unusual adverse event was recorded. Limitations of the study include its retrospective nature and limited size. Hypofractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in patients who previously failed anti-PD-1 therapy. Controlled studies are needed.
接受抗 PD-1 单药治疗后进展的晚期黑色素瘤患者选择有限。我们分析了 2015 年 4 月至 2017 年 12 月期间在一个转诊中心接受抗 PD-1 单药治疗的 133 例晚期黑色素瘤患者队列，包括 26 例经证实进展（PD）或稳定疾病的患者，这些患者在未修改的抗 PD-1 mAb 方案中接受了额外的放射治疗。肿瘤评估在放射治疗和非放射治疗（RECIST 1.1）病变中进行，放射野外的部分（PR）或完全缓解（CR）定义为远隔效应。主要终点是放射治疗和非放射治疗病变的 CR+PR 率。次要终点是无进展生存期（PFS）、黑色素瘤特异性生存期（MSS）和安全性。首次晚期放疗，包括分割放疗（3-5 次，20-26Gy）、标准姑息放疗或脑部放射手术，分别在 23、2 和 1 名患者接受抗 PD-1 治疗后 6.3 个月、2 个月和 1 个月开始。最佳反应为 8 例（31%）CR、2 例（8%）深度 PR 可切除残留转移灶和 16 例（62%）PD。35%的患者出现远隔效应。自抗 PD-1 治疗开始以来，中位 PFS 和 MSS 分别为 15.2 [95%CI：8.0 未达到（na）]和 35.3 [95%CI：18.5 na]个月。PFS 曲线似乎达到了一个平台。在 10 例无残留可评估疾病的患者中，我们停止了抗 PD-1 治疗，在停止抗 PD-1 治疗后 10 个月观察到 1 例复发。未记录到异常不良事件。该研究的局限性包括其回顾性和样本量有限。分割放疗可能增强先前接受抗 PD-1 治疗后进展的患者的抗 PD-1 单药疗效。需要进行对照研究。
