Clinical outcomes in patients with mismatch repair-deficient colorectal cancer: A retrospective real-world evaluation in a single tertiary cancer centre.

Abstract

e23301 Background: Approximately 15% of all patients (pts) with colorectal cancer (CRC) harbour mismatch repair deficiency (dMMR). Although the advent of immune checkpoint inhibitors (ICIs) has significantly improved clinical outcomes in both early and advanced stages of disease, subsets of pts are still resistant to ICIs and real-world evaluation of outcomes is lacking. Methods: We retrospectively analysed the clinico-pathological characteristics, treatment and outcomes of pts with dMMR CRC diagnosed from June 2010 to May 2024 and managed at University College London Hospital. The survival analysis cut-off date was 20 th September 2024. Results: We identified 87 pts (42 female, 45 male) of which 29% had Lynch syndrome. At diagnosis, 57 were non-metastatic (M0) and 30 metastatic (M1) with a median age of 53 (range 18-81); 47% (41/87) were enrolled on immunotherapy trials. For M0 pts, 91% had bowel resection; 44% received neoadjuvant treatment (84% ICIs) and 39% adjuvant chemotherapy. With median follow-up of 29.4 months (IQR 16.0-73.0), 44% (25/57) of M0 pts relapsed and 16% (9/57) had died. Median disease-free survival and median overall survival (mOS) were 30.3 (95% CI 19.2-65.0) and 104.9 (78.4-NR) months. Pts M1 at diagnosis (N = 30) and pts M0 at diagnosis who relapsed with M1 disease (N = 25) were included in the survival analysis of the M1 cohort. Primary treatment comprised either ICIs (69%) or chemotherapy +/- targeted antibodies (31%). At a median follow-up of 51.2 months (IQR 32.5-82.6),33% (18/55) had died. Median progression free survival (PFS) was 26.5 months (95% CI 12.5-NR) and mOS 95 months (95% CI 78.40-NR) respectively. For the 38 patients treated with 1 st line ICIs, median PFS was not reached and 2 year PFS was 71,8% (95% CI 53.8-83.8). The ICI toxicity profiles were consistent with trial data. Conclusions: This retrospective study shows that ICIs are being offered to pts with early and late stage dMMR/MSI-H CRC with outcomes that are consistent or superior to trial outcomes. To optimise real world outcomes all patients should be discussed at a Tumour Board to ensure current diagnosis of dMMR/MSI-H status, accurate staging so that multimodality therapies including surgery, ablation and clinical trials are offered timely and appropriate. Further research is required to identify biomarkers resistance to ICI.