Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY.
Unit of Melanoma Medical Oncology, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
J Clin Oncol. 2024 Nov;42(31):3702-3712. doi: 10.1200/JCO.23.01448. Epub 2024 Aug 5.
In phase III CheckMate 238, adjuvant nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with resected stage IIIB-C/IV melanoma without a significant difference in overall survival (OS). Here, we investigate progression-free survival (PFS) and OS after postrecurrence systemic therapy.
Patients 15 years or older with resected stage IIIB-C/IV melanoma were stratified by stage and tumor PD-L1 status and randomly assigned to receive nivolumab 3 mg/kg every 2 weeks, or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks for 1 year or until disease recurrence, unacceptable toxicity, or withdrawal of consent. Patients with recurrence in each group were assessed for PFS and OS from subsequent systemic therapy (SST) initiation per recurrence timing (≤12 months [early] >12 months [late] from initial therapy).
Recurrences occurred in 198 (44%) of 453 nivolumab-treated patients (122 early, 76 late) and 232 (51%) of 453 ipilimumab-treated patients (160 early, 72 late). Median PFS on next-line systemic therapy for nivolumab-treated patients recurring early versus late was 4.7 versus 12.4 months (24-month rates, 16% 31%); median OS was 19.8 versus 42.8 months (24-month rates: 37% 73%). In response to subsequent therapy, patients on nivolumab with late versus early recurrence were more likely to benefit from anti-PD-1 monotherapy. Nivolumab-treated patients with either an early or late recurrence benefitted from an ipilimumab-based therapy or targeted therapy, each with similar OS.
Postrecurrence survival was longer for patients who recurred >12 months. Patients on nivolumab who recurred early benefitted from SST but had better survival with ipilimumab-based regimens or targeted therapy compared with anti-PD-1 monotherapy.
在 III 期 CheckMate 238 中，与伊匹单抗相比，辅助 nivolumab 显著改善了 IIIB-C/IV 期黑色素瘤患者的无复发生存率，而总生存期（OS）无显著差异。在这里，我们研究了复发后的系统治疗后无进展生存期（PFS）和 OS。
15 岁及以上接受 IIIB-C/IV 期黑色素瘤切除术的患者按分期和肿瘤 PD-L1 状态分层，并随机分配接受 nivolumab 3 mg/kg，每 2 周一次，或 ipilimumab 10 mg/kg，每 3 周一次，共 4 次，然后每 12 周一次，持续 1 年或直至疾病复发、不可接受的毒性或同意书撤回。每组中出现复发的患者根据复发时间（初始治疗后≤12 个月[早期]和＞12 个月[晚期]）从随后的系统治疗（SST）开始评估 PFS 和 OS。
nivolumab 治疗的 453 例患者中有 198 例（44%）发生复发（122 例早期，76 例晚期），ipilimumab 治疗的 453 例患者中有 232 例（51%）发生复发（160 例早期，72 例晚期）。nivolumab 治疗的早期复发患者和晚期复发患者接受下一线系统治疗的中位 PFS 分别为 4.7 个月和 12.4 个月（24 个月时的生存率分别为 16%和 31%）；中位 OS 分别为 19.8 个月和 42.8 个月（24 个月时的生存率分别为 37%和 73%）。在后续治疗中，晚期复发的 nivolumab 治疗患者比早期复发的患者更有可能从抗 PD-1 单药治疗中获益。无论复发时间是早期还是晚期，接受 nivolumab 治疗的患者都受益于伊匹单抗为基础的治疗或靶向治疗，每种治疗的 OS 相似。
复发后 12 个月以上的患者生存时间更长。早期复发的 nivolumab 治疗患者受益于 SST，但与抗 PD-1 单药治疗相比，接受伊匹单抗为基础的治疗或靶向治疗的患者生存时间更长。
