569P - Mismatch repair deficient, stage II/III rectal cancer: Real-world patient, tumour, and treatment characteristics in the Netherlands

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 six 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. Reported evidence on clinical differences between dMMR vs pMMR stage II/III RC is limited. Using real-world data from the Netherlands, the primary aim was to describe and compare patient and tumour characteristics and associated treatments for patients with dMMR vs pMMR stage II/III RC.

Methods

This retrospective real-world analysis of patients with stage II/III RC treated between 2015 and 2022 with known MMR status used data from the Netherlands Cancer Registry. Baseline characteristics and treatment patterns of patients with dMMR and pMMR tumours were compared.

Results

Among 7939 patients included, 184 (2.3%) had dMMR tumours. Compared with pMMR, patients with dMMR were younger (mean age 57.0 vs 61.5 years, P<0.001) and had differences in tumour differentiation grades (18.8% vs 6.1% poor differentiation, P<0.001), histology (mucinous or signet cell adenocarcinoma 12.0% vs 5.2%, P<0.001), tumour cT stage (cT4B 16.8% vs 9.3%, P=0.006), tumour cN stage (cN2 41.3% vs 29.6%, P=0.006), and BRAF mutation status (18.5% vs 7.2% mutation positive, P<0.001). No significant difference was observed in treatment patterns between dMMR and pMMR RC (P=0.19), with neoadjuvant treatment followed by resection being most common in both cohorts (58.2% vs 58.8%).

Conclusions

dMMR RC is rare, and patient and tumour characteristics significantly differ between patients with dMMR and pMMR tumours. Despite dMMR patients having more risk factors associated with poorer outcomes, patients currently receive the same treatment modalities in the Netherlands. Future analyses will focus on differences in clinical outcomes, treatment efficacy, and patient-reported outcomes between matched dMMR and pMMR RC patients to aid interpretation of ongoing clinical trials with immunotherapy for stage II/III dMMR RC.

Clinical trial identification

Editorial acknowledgement

Editorial assistance provided by Hayley Butler, PhD, of Fishawack Indicia, part of Avalere Health.

Legal entity responsible for the study

University Medical Center Utrecht.

Funding

GSK (Study 219473).

Disclosure

I.A. Franken: Financial Interests, Institutional, Research Grant: DoMore Diagnostics. F.H. van der Baan: Financial Interests, Institutional, Research Funding: Personal Genomic Diagnostics. G. Vink: Financial Interests, Institutional, Research Grant: BMS, Merck, Servier, Personal Genome Diagnostics, Bayer, Sirtex, Pierre Fabre, Delfi Diagnostics, Natera. M. Koopman: Financial Interests, Institutional, Advisory Board: Eisai, Nordic Farma, Merck Serono, Pierre Fabre, Servier; Financial Interests, Institutional, Research Grant, Institutional scientific grant: Bayer, Bristol Myers-Squibb, Merck, Personal Genome Diagnostics, Pierre Fabre, Roche, Sirtex, Servier; Financial Interests, Institutional, Principal Investigator: Servier; Non-Financial Interests, Institutional, Other, Chair: ESMO RWD-DH working group; Non-Financial Interests, Institutional, Other, Co-chair: DCCG; Non-Financial Interests, Institutional, Principal Investigator: PLCRC. M. Intven: Financial Interests, Personal, Full or part-time Employment: UMC Utrecht; Non-Financial Interests, Personal, Leadership Role: Dutch Society for Radiotherapy and Oncology; Financial Interests, Institutional, Project Lead: Dutch Cancer Society; Financial Interests, Institutional, Research Funding: Dutch Cancer Society; Financial Interests, Institutional, Research Grant: Dutch Cancer Society; Financial Interests, Personal and Institutional, Invited Speaker: Elekta; Financial Interests, Personal and Institutional, Steering Committee Member: Elekta. S.H. Boklage: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks or ownership: GSK. J. Garside: Financial Interests, Institutional, Full or part-time Employment: GSK. R.V. Wuijtswinkel: Financial Interests, Personal, Full or part-time Employment: GSK. J.M.L. Roodhart: Financial Interests, Institutional, Advisory Board: BMS, Merck-Serono, Amgen, Bayer, Servier, GSK, Nutricia; Financial Interests, Institutional, Invited Speaker: Amgen, Servier, BMS; Financial Interests, Institutional, Research Grant: Bayer, GSK, Servier, Cleara, HUB 4 Organoids, Pierre Fabre, Xilis, DoMore Diagnostics, Delphi, PGDx; Financial Interests, Institutional, Member of Board of Directors: Foundation Hubrecht Organoid Biobank; Financial Interests, Institutional, Principal Investigator: Amgen, GSK, BMS, Pfizer, Nutricia. All other authors have declared no conflicts of interest.