Clinical evidence for efficacy of pembrolizumab in MSI-H and TMB-H advanced solid tumor - results from three cancer centers in China

Sep 21, 2026

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Background: Pembrolizumab is indicated for solid tumors with high-frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H), but effectiveness in real-world practice, with or without chemotherapy, within this molecular subset remains insufficient. Methods: A retrospective analysis of 116 patients receiving pembrolizumab with or without chemotherapy assessed objective response rate and progression-free survival. Results: ORR was 52.6%, with median PFS 14.0 months first-line. Safety showed treatment-related adverse events in 27.6% without treatment-related fatal events. Conclusion: Provides real-world evidence for clinical effectiveness across MSI-H and TMB-H advanced solid cancers.

LanguageEnglish

CategoryHealthcare

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Abstract

Background

Methods

Results

Conclusion

Introduction

Immune checkpoint inhibitors and MSI-H/dMMR

Biomarker assessment and prevalence

Prior pembrolizumab efficacy data

Role of TMB-H

Cancer Immunology, Immunotherapy (2024) 73:74 [https://doi.org/10.1007/s00262-024-03660-2](https://doi.org/10.1007/s00262-024-03660-2) Clinical evidence for efficacy of pembrolizumab in MSI‑H and TMB‑H advanced solid tumor: results from three cancer centers in China Huan Yan1,2 · Lianxi Song1,2,3 · Yizhi Li1 · Qinqin Xu4 · Wenhuan Guo5 · Shaoding Lin6 · Wenjuan Jiang1 · Zhan Wang1 · Li Deng1 · Zhe Huang1 · Haoyue Qin1,2 · Xing Zhang1,2 · Fan Tong7 · Ruiguang Zhang7 · Zhaoyi Liu8 · Lin Zhang9 · Juan Yu10 · Xiaorong Dong7 · Qian Gong11 · Jun Deng12 · Xue Chen12 · Jing Wang12 · Gao Zhang13 · NongYang1,2 · Yongchang Zhang1,2,12,14 · Liang Zeng1 Received: 25 December 2023 / Accepted: 21 February 2024 © The Author(s) 2024 Abstract Background Pembrolizumab has been indicated in the treatment of solid tumors with high frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); however, real-world data on the effectiveness of pembrolizumab with or without chemotherapy in this molecular subset remain limited. Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H. Methods This retrospective study analyzed data from 116 patients with MSI-H or TMB-H advanced solid cancers who received pembrolizumab with or without chemotherapy regardless of treatment setting. We analyzed objective response rate (ORR) and progression-free survival (PFS) . Results The top three cancer types were colorectal (48.6% MSI-H, 6.5% TMB-H), lung (15.4% MSI-H, 84.4% TMB-H), and gastric (15.4% MSI-H, 5.1% TMB-H) . The ORR with pembrolizumab was 52.6%, including complete response (CR) observed in 8.6%(n = 10) of cases and partial responses (PR) in 43.9%(n = 51) . Of the 93 patients who received first-line pembrolizumab, 52 patients achieved objective response (10 CR, 42 PR), with a median PFS of 14.0 months (95% confidence intervals [CI] 6.6–21.4). Of the 23 who received subsequent-line pembrolizumab, the ORR was 39.1%, disease control rate was 91.3%, and median PFS was 5.7 months (95% CI 3.9–7.5). Treatment-related adverse events were observed in 32 patients (27.6%), with no reported treatment-related fatal adverse events. Conclusion Our study provides real-world evidence on the clinical effectiveness of pembrolizumab with or without chemotherapy in the treatment of patients with MSI-H and TMB-H advanced solid cancers. Keywords Pembrolizumab · Microsatellite instability · Tumor mutational burden · MSI-H · Immune checkpoint inhibitor · Solid tumor Abbreviations CR Complete response CRC Colorectal cancer dMMR Mismatch repair deficient ECOG Eastern Cooperative Oncology Group FDA US Food and Drug administration ICI Immune checkpoint inhibitor IHC Immunohistochemistry irAE Immune-related adverse events MSI-H High-frequency microsatellite instability NGS Next-generation sequencing ORR Objective response rate OS Overall survival PD-1 Programmed cell death 1 protein PD-L1 TPS Programmed death-ligand 1 tumor proportion score PFS Progression-free survival PR Partial response TMB-H High tumor mutational burden Huan Yan, Lianxi Song and Yizhi Li have contributed equally to this work and should be regarded as co-first authors. Extended author information available on the last page of the article Introduction The development of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape for patients with advanced solid tumors [1] . In 2015, Le et al. reported their preliminary findings demonstrating the robust response of patients with microsatellite instability-high (MSI-H) to pembrolizumab, an inhibitor of the immune checkpoint component programmed cell death 1 protein (PD-1), after the failure of conventional therapy [2] . The remarkable efficacy observed in their study expedited the approval of pembrolizumab for the treatment of adult and pediatric patients with unresectable/metast

FAQs

What patient population was evaluated in this retrospective study?

The study analyzed 116 patients with advanced solid cancers characterized by either MSI-H or TMB-H who received pembrolizumab with or without chemotherapy.

What were the key efficacy outcomes reported?

Overall response rate (ORR) was 52.6% overall, with complete responses and partial responses reported, and median progression-free survival (PFS) of 14.0 months in the first-line subgroup.

How was safety assessed, and were treatment-related fatal events reported?

Treatment-related adverse events occurred in 32 patients (27.6%). No treatment-related fatal adverse events were reported.

Sep 21, 2026

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