微卫星不稳定性
彭布罗利珠单抗
队列
结直肠癌
耐受性
医学
临床终点
无进展生存期
外科
癌症
肿瘤科
不利影响
内科学
微卫星
化疗
临床试验
免疫疗法
基因
等位基因
生物化学
化学
作者
Dung T. Le,Luis A. Díaz,Tae Won Kim,Éric Van Cutsem,Ravit Geva,Dirk Jäger,Hiroki Hara,Matthew Burge,Bert H. O’Neil,Petr Kavan,Takayuki Yoshino,Rosine Guimbaud,Hiroya Taniguchi,Elena Élez,Salah-Eddin Al-Batran,Patrick M. Boland,Yi Cui,Pierre Leconte,Patricia Marinello,André Thewis
标识
DOI:10.1016/j.ejca.2023.02.016
摘要
Background Pembrolizumab demonstrated durable clinical benefit and manageable safety in previously treated advanced or metastatic microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) colorectal cancer (CRC) in the phase 2 KEYNOTE-164 study. Results from the final analysis are presented. Methods Eligible patients had unresectable or metastatic MSI-H/dMMR CRC and ≥2 prior systemic therapies (cohort A) or ≥1 prior systemic therapy (cohort B). Patients received pembrolizumab 200 mg intravenously every 3 weeks for ≤35 cycles. The primary end-point was objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors, version 1.1 by blinded independent central review. Secondary end-points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability. Results Sixty-one patients in cohort A and 63 patients in cohort B were enroled; median follow-up was 62.2 months and 54.4 months, respectively. ORR was 32.8% (95% CI, 21.3%–46.0%) in cohort A and 34.9% (95% CI, 23.3%–48.0%) in cohort B. Median DOR was not reached (NR) in either cohort. Median PFS was 2.3 months (95% CI, 2.1–8.1) in cohort A and 4.1 months (95% CI, 2.1–18.9) in cohort B. Median OS was 31.4 months (95% CI, 21.4–58.0) in cohort A and 47.0 months (95% CI, 19.2–NR) in cohort B. No new safety signals were observed. Nine patients who initially responded experienced disease progression off therapy and received second-course pembrolizumab. Six patients (66.7%) completed an additional 17 cycles of pembrolizumab, and 2 patients achieved a partial response. Conclusions Pembrolizumab continued to show durable antitumor activity, prolonged OS, and manageable safety in patients with previously treated MSI-H/dMMR CRC. Clinical Trial Registry Information ClinicalTrials.gov, NCT02460198
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