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Introduction <p>KEYNOTE-158 (NCT02628067) supported the US Food and Drug Administration approval of pembrolizumab for microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) advanced solid tumors. Incidence of MSI-H/dMMR tumors in patients of Chinese descent is similar to that of Western populations. Cohort&#xa0;L of KEYNOTE-158 evaluated pembrolizumab in patients of Chinese descent with previously treated MSI-H/dMMR tumors. We previously reported an objective response rate (ORR) of 70% in 20 patients from cohort&#xa0;L which supported the approval in China of pembrolizumab in patients with MSI-H/dMMR solid tumors. Here we present results of the final analysis for 30 patients with median follow-up of 18&#xa0;months.</p> Methods <p>Eligible patients who had confirmed unresectable or metastatic MSI-H/dMMR tumors, and one or more prior lines of therapy, received 200&#xa0;mg pembrolizumab Q3W (up to 35 cycles) until progression, toxicity, or withdrawal. Primary endpoint was ORR per RECIST&#xa0;1.1 by central review. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.</p> Results <p>Thirty patients were enrolled; 7 (23%) were aged ≥ 65&#xa0;years, and 20 (67%) were female. With median follow-up of 18&#xa0;months, ORR was 66.7%. Median DOR was not reached (NR), with 12-month DOR rate of 85.9%. Median PFS was NR, with 18-month PFS rate of 63.0%. Median OS was NR, with 18-month OS rate of 78.8%. Treatment-related adverse events (AE) were reported in 22 (73%) patients. Grade&#xa0;3–4 treatment-related AEs occurred in 7 (23%) patients. Immune-mediated AEs occurred in 11 (37%) patients of which 2 (7%) had grade&#xa0;3 AEs. No grade ≥ 4 immune-mediated AEs occurred.</p> Conclusion <p>Pembrolizumab continues to provide clinically meaningful antitumor activity and durable responses with a manageable safety profile in patients of Chinese descent with MSI-H/dMMR advanced solid tumors. These results are consistent with those reported for patients in the global population and further support the use of pembrolizumab in patients of Chinese descent with MSI-H/dMMR tumors.</p> Trial&#xa0;Registration&#xa0;Number <p>NCT02628067.</p>

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Pembrolizumab in Patients of Chinese Descent with Microsatellite Instability-high/Mismatch Repair Deficient Advanced Solid Tumors: KEYNOTE-158 Final Analysis

  • 期刊论文

  • 发表日期：

    2025年3月22日

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  • Xiaohua Wu,
  • Yimin Mao,
  • Nong Xu,
  • Yuxian Bai,
  • Dong Wang,
  • Xiaojun Chen,
  • Xianli Yin,
  • Yanhong Deng,
  • Jianwei Yang,
  • Jieqing Zhang,
  • Jie Tang,
  • Yi Huang,
  • Jiayi Li,
  • Suxia Luo,
  • Hong Zheng,
  • Weidong Zhao,
  • Miaomiao Xu,
  • Nan Li,
  • Yixiang Mao,
  • Alexander Gozman,
  • Jianming Xu

摘要

Introduction

KEYNOTE-158 (NCT02628067) supported the US Food and Drug Administration approval of pembrolizumab for microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) advanced solid tumors. Incidence of MSI-H/dMMR tumors in patients of Chinese descent is similar to that of Western populations. Cohort L of KEYNOTE-158 evaluated pembrolizumab in patients of Chinese descent with previously treated MSI-H/dMMR tumors. We previously reported an objective response rate (ORR) of 70% in 20 patients from cohort L which supported the approval in China of pembrolizumab in patients with MSI-H/dMMR solid tumors. Here we present results of the final analysis for 30 patients with median follow-up of 18 months.

Methods

Eligible patients who had confirmed unresectable or metastatic MSI-H/dMMR tumors, and one or more prior lines of therapy, received 200 mg pembrolizumab Q3W (up to 35 cycles) until progression, toxicity, or withdrawal. Primary endpoint was ORR per RECIST 1.1 by central review. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results

Thirty patients were enrolled; 7 (23%) were aged ≥ 65 years, and 20 (67%) were female. With median follow-up of 18 months, ORR was 66.7%. Median DOR was not reached (NR), with 12-month DOR rate of 85.9%. Median PFS was NR, with 18-month PFS rate of 63.0%. Median OS was NR, with 18-month OS rate of 78.8%. Treatment-related adverse events (AE) were reported in 22 (73%) patients. Grade 3–4 treatment-related AEs occurred in 7 (23%) patients. Immune-mediated AEs occurred in 11 (37%) patients of which 2 (7%) had grade 3 AEs. No grade ≥ 4 immune-mediated AEs occurred.

Conclusion

Pembrolizumab continues to provide clinically meaningful antitumor activity and durable responses with a manageable safety profile in patients of Chinese descent with MSI-H/dMMR advanced solid tumors. These results are consistent with those reported for patients in the global population and further support the use of pembrolizumab in patients of Chinese descent with MSI-H/dMMR tumors.

Trial Registration Number

NCT02628067.