Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma.

IF 42.1 1区医学 Q1 ONCOLOGY Journal of Clinical Oncology Pub Date : 2024-11-06 DOI:10.1200/JCO.24.00400

Georgina V Long, James Larkin, Dirk Schadendorf, Jean-Jacques Grob, Christopher D Lao, Iván Márquez-Rodas, John Wagstaff, Céleste Lebbé, Jacopo Pigozzo, Caroline Robert, Paolo A Ascierto, Victoria Atkinson, Michael A Postow, Michael B Atkins, Mario Sznol, Margaret K Callahan, Suzanne L Topalian, Jeffrey A Sosman, Srividya Kotapati, Pratik K Thakkar, Corey Ritchings, Melanie Pe Benito, Sandra Re, Samira Soleymani, F Stephen Hodi

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引用次数: 0

Abstract

Purpose: 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.

Methods: 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.

Results: 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 BRAF-mutant and BRAF-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.

Conclusion: 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.

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晚期黑色素瘤患者使用 Nivolumab 加 Ipilimumab 或 Nivolumab 单药的汇总长期疗效。

目的：Nivolumab（NIVO）+ ipilimumab（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疗效。本分析报告介绍了在所有主要公司赞助的试验中，免疫检查点抑制剂（ICI）治疗无效的不可切除/转移性黑色素瘤患者使用联合疗法或单一疗法的长期总生存率（OS），以及与生存率相关的临床因素：对接受NIVO + IPI（NIVO 1 mg/kg + IPI 3 mg/kg或NIVO 3 mg/kg + IPI 1 mg/kg）或NIVO单药治疗（3 mg/kg）的ICI治疗无效患者的六项CheckMate研究数据进行了汇总。对每种治疗方法以及特定亚组的 OS 进行了评估。在治疗组内进行了Cox比例多变量分析（MVA）和分类与回归树（CART）分析：结果：接受NIVO + IPI治疗的患者的OS中位随访时间为45.0个月（n = 839），接受NIVO治疗的患者的OS中位随访时间为35.8个月（n = 536）。NIVO+IPI与NIVO单药相比，OS更长（危险比为0.78 [95% CI，0.67至0.91]），6年OS率分别为52%和41%。在BRAF突变型和BRAF野生型患者以及乳酸脱氢酶（LDH）正常和升高的患者中观察到一致的获益。在不同PD-L1表达水平的患者中也观察到了OS的数值差异，但无PD-L1表达/低PD-L1表达的患者更为明显。在MVA和CART分析中，与生存率下降相关的临床因素有：两种疗法中的LDH均>正常值上限；NIVO+IPI疗法中的年龄≥65岁；NIVO单药疗法中的肝转移：在这项大型、汇总的非随机回顾性分析中，我们观察到，在ICI治疗无效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疗法的生存期相关的临床因素，这可能有助于治疗决策的制定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.