Immunotherapy as conversion therapy

Preliminary studies in locally advanced colon cancer (CRC) with microsatellite instability-high (MSI-H) due to deficiency of the DNA mismatch repair (dMMR) system show that neoadjuvant immunotherapies are suitable as conversion therapy. Most of the patients examined were able to undergo surgery after short-term immunotherapy. Whether the remarkable responses to immune checkpoint inhibitors (ICIs) can be reproduced outside studies in a tertiary center and not only in locally advanced CRC but also in oligometastatic disease was examined using 4 cases in a Spanish clinic.

To determine the best treatment sequence in advanced CRC, detection of KRAS, NRAS, and BRAF mutations as well as dMMR and subsequent testing for MSI-H are mandatory. dMMR/MSI-H status is found in 5-15% of all CRC patients and is a reliable biomarker of long-term response to immune checkpoint inhibitors.

The role of immunotherapy in neoadjuvant therapy has not yet been fully elucidated by randomized trials, although some insights in this area have been gained in recent years. This study presents 4 case reports: 2 of unresectable locally advanced CRC and 2 of oligometastatic CRC, including one with nonlocalized nodal disease and one with liver recurrence. They all responded very well to pembrolizumab monotherapy. This makes the study one of the first to report a complete response (pCR) or robust pathological response (MPR) in oligometastatic disease.