Sorbonne Université and Department of Medical Oncology, Hôpital Saint Antoine, Assistance Publique Hôpitaux de Paris, Paris, France; Equipe Inserm Instabilité des Microsatellites et Cancer, UMRS 938-Centre de Recherche Saint-Antoine, Paris, France.
Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Ann Oncol. 2022 Oct;33(10):1052-1060. doi: 10.1016/j.annonc.2022.06.008. Epub 2022 Jun 25.
In the phase II multicohort CheckMate 142 study, nivolumab plus low-dose (1 mg/kg) ipilimumab provided robust and durable clinical benefit with a manageable safety profile in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) at 13.4- and 25.4-month median follow-up (Overman MJ, Lonardi S, Wong KYM et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36:773-779. Overman MJ, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: long-term follow-up. J Clin Oncol. 2019;37:635). Here, we present results from the 4-year follow-up of these patients.
Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression. Primary endpoint was investigator-assessed objective response rate (ORR; as per RECIST version 1.1).
A total of 119 patients were treated; 76% had ≥2 prior lines of therapy. Median follow-up was 50.9 months (range 46.9-62.7 months). Median duration of therapy was 24.9 months [95% confidence interval (CI) 15.8-33.2 months]. Investigator-assessed ORR increased from 55% (95% CI 45% to 64%) at 13.4 months to 65% (95% CI 55% to 73%) at 50.9 months with a disease control rate of 81% (95% CI 72% to 87%). The complete response rate increased from 3% at 13.4 months to 13% at 50.9 months. Partial responses were observed in 52% of patients; 21% had stable disease, and 12% had progressive disease. Median time to response was 2.8 months (range 1.1-37.1 months), and median duration of response was not reached (range 1.4+ to 58.0+ months). At data cut-off, 37 (48%) patients had ongoing responses. Median progression-free survival was not reached [95% CI 38.4 months-not estimable (NE)], and median overall survival was not reached (95% CI NE). Grade 3-4 treatment-related adverse events (TRAEs) were observed in 32% of patients; 13% of patients had any-grade TRAEs leading to discontinuation.
The results confirm long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC. The safety profile was manageable with no new safety signals.
在 CheckMate 142 期多队列 2 期研究中，纳武利尤单抗联合低剂量（1mg/kg）伊匹单抗在先前接受治疗的微卫星不稳定性高/错配修复缺陷（MSI-H/dMMR）转移性结直肠癌（mCRC）患者中提供了强大且持久的临床获益，并且具有可管理的安全性，在中位随访 13.4 和 25.4 个月时（Overman MJ、Lonardi S、Wong KYM 等人。纳武利尤单抗联合伊匹单抗在 DNA 错配修复缺陷/微卫星高度不稳定的转移性结直肠癌中的持久临床获益。J Clin Oncol。2018;36:773-779. Overman MJ、Lonardi S、Wong KYM、等。纳武利尤单抗联合低剂量伊匹单抗治疗微卫星不稳定性高/错配修复缺陷转移性结直肠癌：长期随访结果。J Clin Oncol。2019;37:635）。在这里，我们介绍了这些患者 4 年随访的结果。
患者接受纳武利尤单抗（3mg/kg）联合低剂量（1mg/kg）伊匹单抗每 3 周（4 剂），随后每 2 周给予纳武利尤单抗（3mg/kg），直至疾病进展。主要终点是研究者评估的客观缓解率（ORR；根据 RECIST 版本 1.1）。
共有 119 名患者接受了治疗；76%的患者有≥2 种既往治疗线。中位随访时间为 50.9 个月（范围为 46.9-62.7 个月）。中位治疗持续时间为 24.9 个月[95%置信区间（CI）15.8-33.2 个月]。研究者评估的 ORR 从 13.4 个月时的 55%（95%CI 45%-64%）增加到 50.9 个月时的 65%（95%CI 55%-73%），疾病控制率为 81%（95%CI 72%-87%）。完全缓解率从 13.4 个月时的 3%增加到 50.9 个月时的 13%。部分缓解见于 52%的患者；21%的患者病情稳定，12%的患者病情进展。中位反应时间为 2.8 个月（范围 1.1-37.1 个月），中位缓解持续时间未达到（范围 1.4+至 58.0+个月）。在数据截止时，37（48%）名患者仍有持续缓解。中位无进展生存期未达到[95%CI 38.4 个月-不可估计（NE）]，中位总生存期未达到（95%CI NE）。观察到 32%的患者出现 3-4 级治疗相关不良事件（TRAEs）；13%的患者出现任何级别 TRAEs 导致停药。
这些结果证实了纳武利尤单抗联合低剂量伊匹单抗在先前接受治疗的 MSI-H/dMMR mCRC 患者中的长期获益。安全性特征可管理，没有新的安全性信号。
