Recent Advances in the Clinical Development of Immune Checkpoint Blockade Therapy for Mismatch Repair Proficient (pMMR)/non-MSI-H Metastatic Colorectal Cancer

James J. Lee, Edward Chu

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations

Abstract

Metastatic colorectal cancer (mCRC) continues to be associated with a poor prognosis, and there remains a significant unmet need for novel agents and treatment regimens. Major breakthroughs have been made with immune checkpoint blockade therapy in several disease types, including DNA mismatch repair deficient/microsatellite instability-high (MSI-H) tumors. To date, however, immune checkpoint monotherapy has not shown significant clinical activity in the treatment of patients with mismatch repair proficient (pMMR)/non-MSI-H mCRC. The immune resistance mechanisms in pMMR/non-MSI-H mCRC have not yet been clearly elucidated. Significant efforts are currently focused on identifying effective combination immunotherapy regimens for the treatment of patients with pMMR/non-MSI-H mCRC. The combination of atezolizumab with cobimetinib had shown promising clinical activity in an early-phase clinical trial. Unfortunately, the IMblaze 370 (COTEZO) phase III trial of atezolizumab/cobimetinib combination in patients with mCRC failed to show significant improvement in overall survival in patients treated with the atezolizumab/combimetinib combination in comparison with regorafenib alone. This review summarizes the recent major advances in the clinical development of immunotherapy regimens for patients with pMMR/non-MSI-H mCRC.

Original languageEnglish (US)
Pages (from-to)258-273
Number of pages16
JournalClinical colorectal cancer
Volume17
Issue number4
DOIs
StatePublished - Dec 2018
Externally publishedYes

Keywords

  • Immunogenic cell death (ICD)
  • Immunotherapy
  • Microsatellite instability
  • PD-1
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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