A comparison of real-world outcomes by mismatch repair status in patients with stage II/III rectal cancer in the Netherlands.

Abstract

260 Background: A subset of rectal tumours (~3–5%) have mismatch repair deficiency (dMMR); the remaining are classified as MMR proficient (pMMR). A recent trial for stage II/III dMMR rectal cancer (RC) showed that 6 months of neoadjuvant treatment with dostarlimab, a programmed cell death protein 1 inhibitor, induced a 100% clinical complete response rate and allowed for organ preservation. Using real-world data from the Netherlands, a dMMR patient cohort was compared to a matched pMMR cohort to assess if clinical outcomes differed, even after matching for baseline characteristics. Methods: Utilizing data from the Netherlands Cancer Registry, this retrospective analysis assessed patients with stage II/III RC treated from 2015–2022 with known MMR status. The dMMR cohort was matched 1:2 to a cohort of pMMR patients on age, year of diagnosis, tumour clinical (cT) stage, and node clinical (cN) stage. Event-free survival (EFS; defined as first occurrence of locoregional failure, distant metastasis, a new primary colorectal tumour, or death from any cause) and overall survival (OS) were compared using Kaplan-Meier methodology and a univariable Cox model. Results: Among the 7939 patients included, 184 (2.3%) had dMMR tumours. After matching and a loss of 8 dMMR patients due to ineligibility, 176 dMMR patients were compared to 363 pMMR patients. Matching successfully removed differences in age, cT, and cN stage; however, dMMR patients continued to have more BRAF mutants (p=0.014), more poorly differentiated tumours (p<0.001) and more variation in histology (p=0.01). dMMR patients had a statistically significant lower risk of experiencing an event (hazard ratio [HR] 0.54 [95% confidence interval (CI) 0.38–0.77], p<0.001), with a 3-year EFS of 79.6% (95% CI 73.7–86.1) compared to pMMR patients (64.7% [95% CI 59.8–70.1]). For OS, there was no significant difference between the dMMR and pMMR cohorts (HR 0.73 [95% CI 0.47–1.16], p=0.181); however, within the small group of patients with an event, OS at 1 year for dMMR patients was 68.4% (95% CI 55.1–84.9) compared to 93.5% (95% CI 89.5–97.7) for pMMR patients (p=0.001). Conclusions: dMMR RC is rare, and tumour characteristics differ from those of patients with pMMR tumours (1). After controlling for clinical stage and age, this study suggests dMMR patients have improved EFS compared to pMMR patients. There is no significant difference in OS between groups but dMMR patients with an event have worse OS than pMMR patients, highlighting an additional need to prevent recurrence of disease within dMMR patients.1. Lunenberg, R et al. Poster presented at ESMO Congress (Presentation 569P), 13-17 Sept 2024, Barcelona, Spain.