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PURPOSE

In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes.

PATIENTS AND METHODS

Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab. Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated.

RESULTS

Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with -mutant tumors and 46%, 42%, and 22% in those with -wild-type tumors, respectively. In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively. Since the 5-year analysis, no new safety signals were observed.

CONCLUSION

These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.

目的

在 III 期 CheckMate 067 试验中，先前已证明纳武利尤单抗联合伊匹单抗和纳武利尤单抗单药治疗与伊匹单抗相比具有持久的临床获益。在此，我们报告 6.5 年的疗效和安全性结果。

患者和方法

先前未经治疗的不可切除的 III 期或 IV 期黑色素瘤患者按 1:1:1 随机分配，分别接受纳武利尤单抗 1 mg/kg 加伊匹单抗 3 mg/kg 每 3 周（4 剂），随后每 2 周（n = 314）、每 2 周（n = 316）纳武利尤单抗 3 mg/kg 或每 3 周（4 剂）伊匹单抗 3 mg/kg（n = 315）。主要终点是纳武利尤单抗联合伊匹单抗或纳武利尤单抗与伊匹单抗相比的无进展生存期和总生存期（OS）。次要终点包括客观缓解率、纳武利尤单抗联合伊匹单抗与纳武利尤单抗单药的描述性疗效评估以及安全性。黑色素瘤特异性生存（MSS；描述性分析），排除与黑色素瘤无关的死亡，也进行了评估。

结果

中位 OS（最小随访时间，6.5 年）分别为联合组、纳武利尤单抗组和伊匹单抗组的 72.1、36.9 和 19.9 个月。中位 MSS 未达到，分别为 58.7、21.9 和 21.9 个月；-突变肿瘤患者的 6.5 年 OS 率分别为 57%、43%和 25%，-野生型肿瘤患者分别为 46%、42%和 22%。在停止治疗的患者中，中位无治疗间隔分别为 27.6、2.3 和 1.9 个月。自 5 年分析以来，未观察到新的安全性信号。