97P - ICI for patients with MSS metastatic colorectal cancer

Background

Colorectal cancer (CRC) is the third most often-diagnosed cancer in both men and women, with more than 1.9 million new cases worldwide in 2020. Immune-checkpoint inhibitors (ICI) show modest activity and efficacy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients harbouring a proficient mismatch repair system (pMMR). However, even the fact that MSS tumours are infiltrated by T cells was proved, they will not respond to therapy with anti-PD-1 mAbs as they do not express ICI but escape from immunosurveillance, for example, by downregulating HLA expression. Importantly, there is a hypothesis that a particular fraction of non-hypermutated MSS tumours might in theory respond to PD-1/PD-L1 blockade therapy. Some trials demonstrated benefits for surveillance for MSS tumours treated by intensive combination of chemotherapy with ICI, but fragile and older patients cannot receive these regimens. Treatment with less toxicity could be the option for some specific group of patients with MSS tumours.

Methods

We performed a retrospective analysis of the efficacy and safety of pembrolizumab and lenvatinib for late-stage colorectal cancer as a salvage line. The Kaplan-Meier method was used to estimate survival distribution and response rate (RR).

Results

There were 20 cases (male:13, female:7), and the median average age was 63 (32-75) years old. The median progression-free survival (PFS) and overall survival (OS) were 4.5 (95%CI;1.4-14) months and 10 (95%CI;2.5-26.4) months, respectively. Response rate (RR) was 16% and disease control rate (DCR) was 25.6%. Also in analysis, Grade 2 or more severe diarrhea was an independent prognostic factor for PFS (p = 0.004) and OS (p < 0.0001). The common treatment-related adverse events were gastrointestinal toxicity and hepatic dysfunction, but they were not severe and no treatment related death was observed.

Conclusions

Even though LEAP-017 was not effective, we suggest that some populations of patients could have benefits from this regimen as a salvage therapy for MSS colorectal cancer. Also, our findings assume that the possibility that Grade 2 or more severe diarrhea may be a predictive factor. In conclusion, we think that further investigations in this field are needed.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.