Lenz Heinz-Josef, Van Cutsem Eric, Luisa Limon Maria, Wong Ka Yeung Mark, Hendlisz Alain, Aglietta Massimo, García-Alfonso Pilar, Neyns Bart, Luppi Gabriele, Cardin Dana B, Dragovich Tomislav, Shah Usman, Abdullaev Sandzhar, Gricar Joseph, Ledeine Jean-Marie, Overman Michael James, Lonardi Sara
USC Norris Comprehensive Cancer Center, Los Angeles, CA.
University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium.
J Clin Oncol. 2022 Jan 10;40(2):161-170. doi: 10.1200/JCO.21.01015. Epub 2021 Oct 12.
Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study.
Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1).
Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including or mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events.
Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.
基于CheckMate 142研究，纳武利尤单抗被美国食品药品监督管理局批准作为单药或与伊匹木单抗联合用于氟尿嘧啶、奥沙利铂和伊立替康治疗后进展的微卫星高度不稳定/错配修复缺陷（MSI-H/dMMR）转移性结直肠癌（mCRC）患者。本文展示了纳武利尤单抗联合低剂量伊匹木单抗在II期CheckMate 142研究一线治疗队列中的结果。
MSI-H/dMMR CRC转移性疾病未接受过先前治疗的患者，每2周接受一次纳武利尤单抗治疗，每6周接受一次低剂量伊匹木单抗治疗，直至疾病进展。主要终点为客观缓解率（研究者评估；RECIST v1.1）。
接受治疗患者的中位年龄为66岁（N = 45）。中位随访时间为29.0个月。客观缓解率和疾病控制率分别为69%（95%CI，53至82）和84%（95%CI，70.5至93.5），完全缓解率为13%。中位缓解持续时间未达到；74%的缓解者在数据截止时仍有持续缓解。中位无进展生存期和中位总生存期未达到，最短随访时间为24.2个月（24个月率分别为74%和79%）。无论基线人口统计学和肿瘤特征如何，包括 或 突变状态，均观察到临床获益。在一项事后分析中，14名停止治疗且未接受后续治疗的患者中，10名仍无疾病进展。患者报告的结局在治疗期间保持稳定。22%的患者发生3-4级治疗相关不良事件；13%的患者因任何级别的治疗相关不良事件而停药。
纳武利尤单抗联合低剂量伊匹木单抗显示出强大且持久的临床获益，作为MSI-H/dMMR mCRC的一线治疗耐受性良好。基于这些有前景的数据，有必要开展随机研究。
