Outcomes following Immune Checkpoint Inhibitor Treatment of Patients with Microsatellite Instability-High Cancers: A Systematic Review and Meta-analysis

Fausto Petrelli, Michele Ghidini, Antonio Ghidini, Gianluca Tomasello

Research output: Contribution to journalReview articlepeer-review


Importance: The mismatch repair (MMR) pathway plays a crucial role in repairing DNA replication errors in normal and cancer cells. Defects in DNA MMR proteins that determine the microsatellite instability-high (MSI-H) condition lead to the accumulation of mutations and the generation of neoantigens, which may stimulate the antitumor immune response. Clinical trials have demonstrated that MSI-H status is associated with long-term benefit in patients treated with immune checkpoint inhibitors (ICIs). Objective: To evaluate the activity of ICIs in terms of overall response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) in patients with MSI-H cancers. Data Sources: Published articles that evaluated ICIs in the treatment of advanced MSI-H tumors from inception to December 2019 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. Study Selection: Prospective or retrospective studies, published in the English language, providing outcome data with ICIs in patients with MSI-H cancer were selected. Data Extraction and Synthesis: Author and year of publication, type of studies, diseases included, median follow up, type of ICI, median OS,and PFS, ORR, DCR and 1-, 2-, and 3-year OS were retrieved. Analysis was performed in December 2019. Main Outcome and Measures: The primary outcome of interest was ORR. Secondary end points were median PFS, median OS, pooled rate of patients alive at 1, 2,and 3 years, and pooled rate of patients that attained disease control rate ([DCR] calculated as the sum of stable disease rate and ORR). Results: Overall, 939 patients (14 studies) were analyzed mainly in pretreated settings. The pooled ORR was 41.5% (95% CI, 34.9%-48.4%). The pooled DCR was 62.8% (95% CI, 54.5%-70.3%). Pooled median PFS was 4.3 months (95% CI, 3-6.8 months). The pooled median OS was 24 months (95% CI, 20.1-28.5 months). The pooled 1- and 2-year OS were 75.6% (95% CI, 61.8%-85.5%) and 56.5% (95% CI, 46%-66.4%), respectively. Because only 1 study provided 3-year OS data, a formal pooled analysis for 3 years was not possible. Conclusions and Relevance: In this meta-analysis of patients with pretreated MSI-H cancer, ICIs were associated with high activity independent of tumor type and drug used. Among molecular biomarkers for selection of treatment, MMR proteins may have a predictive value for the activity of immunotherapy.

Original languageEnglish
Pages (from-to)1068-1071
JournalJAMA oncology
Issue number7
Publication statusPublished - 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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