Refractory microsatellite-stable metastatic colorectal cancer: a comparison between botensilimab + balstilimab and...

The combination of botensilimab + balstilimab demonstrated promising clinical activity in heavily pre-treated patients with microsatellite-stable metastatic colorectal cancer (mCRC) in a recently published phase I study (NCT03860272).

Our objective was to derive overall survival (OS), progression-free survival (PFS) and safety data from the trials of reference of the current standard of care for refractory mCRC and from the above-mentioned study, and to compare them. After a systematic search of PubMed, we selected four studies (SUNLIGHT, FRESCO-2, RECOURSE, CORRECT). Individual patient OS and PFS data were extracted from Kaplan-Meier curves and more frequent toxic effect rates were collected.

Immunotherapy showed higher efficacy in terms of median OS both compared with trifluridine-tipiracil plus bevacizumab [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.44-0.89] and to later lines of treatment: fruquintinib, regorafenib, and trifluridine-tipiracil alone. These results were confirmed by median PFS comparison of all the therapies except for the trifluridine-tipiracil + bevacizumab combination (HR 0.46, 95% CI 0.35-0.61 in favor of trifluridine-tipiracil + bevacizumab). As for treatment-related adverse events the most frequent with immunotherapy were fatigue and diarrhea. The other regimens were associated with hematologic toxic effects, nausea, hypertension, and dermatological toxicity.

These findings suggest that the immunotherapy combination appears to be a potential option for patients with refractory mCRC while being associated with a completely different toxicity profile. However, confirmation of its efficacy awaits the results of randomized studies. Better comprehension of disease characteristics related to treatment response, such as metastatic sites and molecular biology, is warranted for patient selection.