628P - Immunotherapy in mismatch repair-deficient metastatic colorectal cancer: Long-term outcome and novel predictive markers

Background

PD-1 with or without CTLA-4 blockade is the treatment of choice in dMMR/MSI-H metastatic colorectal cancer (mCRC) patients. However, there are currently no validated predictors for treatment response, and there is a paucity of real-world data on treatment efficacy. Our aim was to assess predictive markers for response to immunotherapy in this patient population.

Methods

A study using two prospective cohorts from the University of Texas MD Anderson Cancer Center and Sheba Medical Center of consecutive patients with dMMR/MSI-H mCRC that were treated with immunotherapy between 2014-2022. Primary outcomes were progression-free survival (PFS) and overall response rate (ORR). Evaluated predictors included ECOG-PS score, RAS/BRAF status, single-agent versus nivolumab plus ipilimumab immunotherapy, metastatic sites, disease burden, and CEA levels prior to treatment initiation. Kaplan-Meier analysis and univariate Cox proportional hazard regression model were used to analyze the effect of all exposure variables on PFS.

Results

The study cohort included 153 patients with a median age of 60 (IQR 45-71), of them 51.6% (n=79) were males. First-line immunotherapy with anti-PD-1 or anti-PD-1 plus anti-CTLA-4 was used in 77.8% (n=119) and 22.2% (n=34) of patients, respectively. Median follow-up time was 26 months (IQR 11-48). Median PFS was 51.6 months (95%CI 38.1-NR) and ORR was 58.1% (n=89). ECOG-PS score ≥2 and ≥3 metastatic sites were associated with worse PFS with a HR of 2.09 (95%CI 0.98-4.47) and 3.11 (95%CI 1.61-6.03), respectively. The presence of liver or lung metastasis, either solitary or mixed sites, were associated with worse PFS with HRs of 2.35 (95%CI 1.43-3.88) and 2.30 (95%CI 1.31-4.04), respectively. Right-sided tumors were associated with improved PFS with a HR of 0.56 (95% CI 0.32-0.97). CEA levels ˃5 μg/L prior to treatment initiation were associated with worse PFS with a HR of 2.23 (95%CI 1.30-3.81).

Conclusions

Liver or lung metastasis, and high CEA levels predict poor response to immunotherapy in dMMR/MSI-H mCRC. Conversely, right-sided tumor predicts improved response.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.