PURPOSE KEYNOTE-164 (NCT02460198) evaluated the antitumor activity of pembrolizumab in previously treated, metastatic, microsatellite instability–high/mismatch repair–deficient (MSI-H/dMMR) colorectal cancer (CRC). METHODS This phase II open-label study involved 128 centers worldwide. Eligible patients were age ≥ 18 years and had metastatic MSI-H/dMMR CRC treated with ≥ 2 prior lines of standard therapy, including fluoropyrimidine, oxaliplatin, and irinotecan with or without anti–vascular endothelial growth factor/epidermal growth factor receptor monoclonal antibody (cohort A) or ≥ 1 prior line of therapy (cohort B). MSI-H/dMMR status was assessed locally. Patients received pembrolizumab 200 mg every 3 weeks for up to 2 years until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate by RECIST version 1.1 by independent central review. Secondary end points were duration of response, progression-free survival (PFS), overall survival, safety, and tolerability. RESULTS A total of 124 patients with MSI-H/dMMR CRC (61 in cohort A, 63 in cohort B) enrolled. At data cutoff, median follow-up was 31.3 months (range, 0.2-35.6 months) for cohort A and 24.2 months (range, 0.1-27.1 months) for cohort B. Objective response rate was 33% (95% CI, 21% to 46%) and 33% (95% CI, 22% to 46%), respectively, with median duration of response not reached in either cohort. Median PFS was 2.3 months (95% CI, 2.1 to 8.1 months) and 4.1 months (95% CI, 2.1 to 18.9 months). Median overall survival was 31.4 months (95% CI, 21.4 months to not reached) and not reached (95% CI, 19.2 months to not reached). Treatment-related grade 3-4 adverse events occurred in 10 patients (16%) in cohort A and 8 (13%) in cohort B, with the most common occurring in ≥ 2 patients being pancreatitis, fatigue, increased alanine aminotransferase, and increased lipase (2 patients each; 3%) in cohort A. CONCLUSION Pembrolizumab is effective with a manageable safety profile in patients with MSI-H/dMMR CRC.

中文翻译：

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Pembrolizumab 在难治性微卫星不稳定性高/错配修复缺陷转移性结直肠癌中的 II 期开放标签研究：KEYNOTE-164

目的 KEYNOTE-164 (NCT02460198) 评估了派姆单抗在先前治疗过的转移性微卫星不稳定性高/错配修复缺陷 (MSI-H/dMMR) 结直肠癌 (CRC) 中的抗肿瘤活性。方法 这项 II 期开放标签研究涉及全球 128 个中心。符合条件的患者年龄 ≥ 18 岁并且患有转移性 MSI-H/dMMR CRC，并且接受了≥ 2 种先前标准疗法的治疗，包括氟嘧啶、奥沙利铂和伊立替康联合或不联合抗血管内皮生长因子/表皮生长因子受体单克隆抗体。队列 A) 或 ≥ 1 个先前的治疗线（队列 B）。MSI-H/dMMR 状态在本地进行评估。患者每 3 周接受一次 pembrolizumab 200 mg，持续长达 2 年，直至出现进展、不可接受的毒性或停药。主要终点是独立中央审查通过 RECIST 1.1 版的客观反应率。次要终点是反应持续时间、无进展生存期（PFS）、总生存期、安全性和耐受性。结果 共纳入 124 名 MSI-H/dMMR CRC 患者（队列 A 中 61 名，队列 B 中 63 名）。在数据截止时，队列 A 的中位随访时间为 31.3 个月（范围，0.2-35.6 个月），队列 B 的中位随访时间为 24.2 个月（范围，0.1-27.1 个月）。客观缓解率为 33%（95% CI，21%） 46%）和 33%（95% CI，22% 至 46%），两个队列中均未达到中位缓解持续时间。中位 PFS 为 2.3 个月（95% CI，2.1 至 8.1 个月）和 4.1 个月（95% CI，2.1 至 18.9 个月）。中位总生存期为 31.4 个月（95% CI，21.4 个月至未达到）和未达到（95% CI，19.2 个月至未达到）。