Pembrolizumab for the treatment of colorectal cancer

ABSTRACT

Introduction: Colorectal cancer (CRC) is one of the most frequent and lethal cancers in the world, and therapies are still insufficient. Immune checkpoint inhibitors (ICI) in metastatic CRC (mCRC) have not revolutionized treatment to the extent that they have in melanoma or renal carcinoma. Their use is limited to a molecular niche of mCRC with microsatellite instability (MSI). This review summarizes clinical data published with pembrolizumab in mCRC and also tries to identify potential new strategies.

Areas covered: This paper focuses on pembrolizumab in mCRC. We screened all trials on PubMed and ClinicalTrials.gov and describe the most significant ones in our opinion.

Expert opinion: Pembrolizumab seems to be effective in tumors with MSI-high status. It defines a new horizon for therapeutic strategy called ‘agnostic’ medicine. For microsatellite stable (MSS) colorectal cancers, the future challenge will be to successfully redraw the immune microenvironment to make it immunogenic with new therapeutic combinations, including ICI.

KEYWORDS:

• Colorectal cancer
• immune checkpoint inhibitors
• pembrolizumab
• tumor mutational burden

Article highlights

• Pembrolizumab is approved in MSI-H tumors, including colorectal cancer.

• Pembrolizumab alone is not effective in MSS colorectal cancer.

• The goal of ongoing trials is to increase the efficacy of pembrolizumab in MSS colorectal cancer by using new combinations with chemotherapy or targeted therapy.

This box summarizes key points contained in the article.

Declaration of interest

J Bennouna has declared honorarium board and educational symposium from MSD, BMS, Astrazeneca, Servier, Roche, Bayer and Boehringer-Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.