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Immune checkpoint inhibition in advanced colorectal cancer with inherited and acquired microsatellite instability:

Constantin A Dasanu1,2, Mohammed Alani3, Shaghayegh Habibi3

  • 1Lucy Curci Cancer Center, Eisenhower Health, Rancho Mirage, CA, USA.

Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners
|May 29, 2023
PubMed

Insights

Advanced colorectal cancer patients with microsatellite instability (MSI) have promising treatment options. Immune checkpoint inhibitor (ICI) therapies, including single-agent and combination regimens, show significant efficacy and are expanding the therapeutic landscape.

Area of Science:

  • Oncology
  • Genetics
  • Immunotherapy

Background:

  • Colorectal cancer (CRC) management is evolving, particularly for advanced stages.
  • Microsatellite instability (MSI) is a critical biomarker in CRC, influencing treatment response.
  • Immune checkpoint inhibitors (ICIs) have emerged as a significant therapeutic class.

Purpose of the Study:

  • To comprehensively review current data on single-agent and combination therapies for advanced colorectal cancer with MSI.
  • To assess the efficacy of immune checkpoint inhibitors (ICIs) in patients with inherited and acquired MSI.
  • To explore the role of biomarkers in predicting treatment response to ICIs.

Main Methods:

  • Systematic literature search of PubMed and MEDLINE databases (inception to December 2022).
  • Inclusion of data from independent sources: U.S. Food and Drug Administration and ClinicalTrials.gov.
  • Analysis of studies evaluating microsatellite stability testing, tumor mutational burden (TMB), and germline mutation analysis.

Main Results:

  • Microsatellite stability testing, TMB, and germline analysis identify patients benefiting from ICI therapy.
  • Single-agent pembrolizumab demonstrates superiority over traditional chemotherapy in MSI-high patients.
  • Nivolumab-ipilimumab is an approved combination ICI therapy; dostarlimab shows promise in refractory dMMR cancers.

Conclusions:

  • The therapeutic landscape for advanced colorectal cancer with MSI is optimistic.
  • Novel and effective ICI drugs and combinations are expanding treatment options.
  • Further research is needed on biomarkers and optimal ICI therapy duration.
Keywords:
Immune checkpoint inhibitorcolorectal cancerdeficient mismatch repairmicrosatellite instabilitytumor mutational burden

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