Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD.
J Clin Oncol. 2024 Nov 20;42(33):3926-3934. doi: 10.1200/JCO.24.01125. Epub 2024 Aug 13.
Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial.
Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory.
After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, -mutant melanoma, and lactate dehydrogenase >2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% 61%) and any-grade TRAEs leading to discontinuation (17% 41%).
Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most-but not all-subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.
纳武利尤单抗联合雷利度胺和纳武利尤单抗联合伊匹单抗分别基于 II/III 期 RELATIVITY-047 和 III 期 CheckMate 067 试验获得晚期黑色素瘤的批准。由于不存在比较这些方案的头对头试验，因此使用每个试验的患者水平数据进行了间接治疗比较。
采用倾向评分治疗加权（IPTW）调整基线特征差异。选择最小随访时间（RELATIVITY-047，33 个月；CheckMate 067，36 个月）以最佳对齐评估。结果包括无进展生存期（PFS）、确认的客观缓解率（cORR）和研究者评估的黑色素瘤特异性生存期（MSS）；总生存期（OS）和治疗相关不良事件（TRAEs）。采用 Cox 回归模型比较 PFS、OS 和 MSS。采用 logistic 回归模型比较 cORR。亚组分析为探索性分析。
在 IPTW 后，纳武利尤单抗联合雷利度胺（n = 339）和纳武利尤单抗联合伊匹单抗（n = 297）的关键基线特征得到平衡。纳武利尤单抗联合雷利度胺的 PFS（风险比 [HR]，1.08 [95%CI，0.88 至 1.33]）、cORR（比值比，0.91 [95%CI，0.73 至 1.14]）、OS（HR，0.94 [95%CI，0.75 至 1.19]）和 MSS（HR，0.86 [95%CI，0.67 至 1.12]）与纳武利尤单抗联合伊匹单抗相似。亚组比较显示，纳武利尤单抗联合伊匹单抗在肢端黑色素瘤、-突变黑色素瘤和乳酸脱氢酶>2×正常值上限的患者中具有更大的数值差异，但受小样本量限制。纳武利尤单抗联合雷利度胺与 3-4 级 TRAE（23%比 61%）和任何等级 TRAE 导致停药（17%比 41%）的发生率较低。
纳武利尤单抗联合雷利度胺在总体人群中的疗效与纳武利尤单抗联合伊匹单抗相似，包括大多数（但不是全部）亚组，并且在未经治疗的晚期黑色素瘤患者中改善了安全性。结果应谨慎解释。
