Long Georgina V, Larkin James, Schadendorf Dirk, Grob Jean-Jacques, Lao Christopher D, Márquez-Rodas Iván, Wagstaff John, Lebbé Céleste, Pigozzo Jacopo, Robert Caroline, Ascierto Paolo A, Atkinson Victoria, Postow Michael A, Atkins Michael B, Sznol Mario, Callahan Margaret K, Topalian Suzanne L, Sosman Jeffrey A, Kotapati Srividya, Thakkar Pratik K, Ritchings Corey, Pe Benito Melanie, Re Sandra, Soleymani Samira, Hodi F Stephen
Melanoma Institute Australia and Royal North Shore and Mater Hospitals, The University of Sydney, Sydney, NSW, Australia.
The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom.
J Clin Oncol. 2025 Mar 10;43(8):938-948. doi: 10.1200/JCO.24.00400. Epub 2024 Nov 6.
Nivolumab (NIVO) + ipilimumab (IPI) combination and NIVO monotherapy have demonstrated durable clinical benefit in patients with unresectable/metastatic melanoma. This analysis describes long-term overall survival (OS) with the combination or monotherapy pooled across all major company-sponsored trials, as well as clinical factors associated with survival, in patients with immune checkpoint inhibitor (ICI) treatment-naïve unresectable/metastatic melanoma.
Data were pooled from six CheckMate studies in ICI treatment-naïve patients receiving NIVO + IPI (NIVO 1 mg/kg + IPI 3 mg/kg or NIVO 3 mg/kg + IPI 1 mg/kg) or NIVO monotherapy (3 mg/kg). OS was assessed for each treatment, as well as in select subgroups. Cox proportional multivariate analysis (MVA) and classification and regression tree (CART) analyses were performed within treatment arms.
Median follow-up for OS was 45.0 months for patients treated with NIVO + IPI (n = 839) and 35.8 months for patients treated with NIVO (n = 536). OS was longer with NIVO + IPI versus NIVO monotherapy (hazard ratio, 0.78 [95% CI, 0.67 to 0.91]), with 6-year OS rates of 52% versus 41%, respectively. Consistent benefit was observed in -mutant and -wild-type patients and those with normal and elevated lactate dehydrogenase (LDH). Numerical difference in OS was also observed across PD-L1 expression levels, although more pronounced with no/low PD-L1 expression. Clinical factors associated with decreased survival in both the MVA and CART analyses were LDH > upper limit of normal with either treatment, age ≥65 years with NIVO + IPI, and the presence of liver metastases with NIVO monotherapy.
In this large, pooled nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment-naïve advanced melanoma and identifies clinical factors that appear to be associated with survival for each treatment, which may assist with treatment decision making.
纳武利尤单抗（NIVO）+伊匹木单抗（IPI）联合疗法和NIVO单药疗法已在不可切除/转移性黑色素瘤患者中显示出持久的临床获益。本分析描述了在所有主要公司赞助的试验中汇总的联合疗法或单药疗法的长期总生存期（OS），以及在初治不可切除/转移性黑色素瘤患者中与生存相关的临床因素，这些患者接受免疫检查点抑制剂（ICI）治疗。
数据来自六项CheckMate研究，这些研究针对初治ICI的患者，他们接受NIVO+IPI（NIVO 1mg/kg+IPI 3mg/kg或NIVO 3mg/kg+IPI 1mg/kg）或NIVO单药疗法（3mg/kg）。对每种治疗以及选定亚组的OS进行了评估。在各治疗组内进行了Cox比例多变量分析（MVA）和分类与回归树（CART）分析。
接受NIVO+IPI治疗的患者（n=839）OS的中位随访时间为45.0个月，接受NIVO治疗的患者（n=536）为35.8个月。NIVO+IPI组的OS长于NIVO单药疗法组（风险比，0.78[95%CI，0.67至0.91]），6年OS率分别为52%和41%。在 -突变型和 -野生型患者以及乳酸脱氢酶（LDH）正常和升高的患者中均观察到一致的获益。在不同的PD-L1表达水平上也观察到OS的数值差异，尽管在无/低PD-L1表达时更为明显。在MVA和CART分析中，与生存降低相关的临床因素包括：两种治疗中LDH>正常上限、NIVO+IPI治疗时年龄≥65岁以及NIVO单药疗法时存在肝转移。
在这项大型汇总的非随机回顾性分析中，我们观察到在初治ICI的晚期黑色素瘤患者中，NIVO+IPI比NIVO提供更长的OS，并确定了似乎与每种治疗的生存相关的临床因素，这可能有助于治疗决策。
