629P - First results of the french prospective cohort of colorectal cancers with microsatellite instability (COLOMIN2)

Background

Colorectal cancers with microsatellite instability/deficient mismatch repair (dMMR/MSI CRC) are associated with particular outcome and treatment, especially in the recent context of immune checkpoint inhibitors (ICI). There is no large prospective real-life cohort evaluating outcome and prognostic factors in dMMR/MSI CRC.

Methods

COLOMIN2 is a prospective, multicenter cohort designed to assess treatment and prognosis of dMMR/MSI CRC. Key eligibility criteria included histologically proven CRC with a MSI (molecular biology) and/or dMMR (immunohistochemistry, IHC) status. The primary endpoint is time to recurrence (TTR) for non-metastatic tumors and progression-free survival (PFS) for metastatic tumors.

Results

Between January 2016 and December 2021, 637 patients were included by 37 centers with stage I (8.2%), II (36.4%), III (35.5%) or IV (18.7%) dMMR/MSI CRC. The mean age was 69.6 years, 59.8% were women and 62.6% were ECOG PS 0 or 1. Most tumors had a MMR IHC (76.1%) and 23.9% a MSI test alone. BRAF and RAS mutations were identified in 44.9% and 25.0%, respectively; with no difference according to tumor stage. One third of patients had a Lynch syndrome with proven MMR gene mutation (32.5%). Most tumors are located in ascending colon (69.5%) and well/moderately differentiated (55.3%). Among stage II and stage III CRC patients 16.9% and 61.7% had adjuvant chemotherapy (CT), respectively; mostly with oxalipatin-based CT (82.6%) whatever the tumor stage. After a median follow-up of 23 months, TTR at 3 years were 97.0% in stage I, 88.6% in stage II and 68.9% in stage III. Most patients with stage IV disease had one metastatic site (74.5%), mostly in liver (48.1%) and peritoneum (36.8%). Most patients were treated by first-line CT +/- targeted therapy (79.8%) and few by ICI (12.9%). Median PFS were 11.8 [95%CI: 7.1-28.0] months and 28.0 [95%CI: 2.1-NA] months for patients treated with CT and IO, respectively.

Conclusions

This real-life cohort confirms the good prognosis of non-metastatic dMMR/MSI CRC by contrast to metastatic patients treated by chemotherapy +/- targeted therapy. Clinical and biological prognostic factors are currently explored, and will be presented during ESMO meeting.

Clinical trial identification

NCT05511688.

Editorial acknowledgement

Legal entity responsible for the study

Fédération francophone de cancérologie digestive.

Funding

Aide au financement d’une COhorte nationale sur les Maladies de l’Appareil Digestif (COMAD) Société Nationale Française de Gastro-Entérologie (SNFGE).

Disclosure

D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Servier, Pierre Fabre. V. Hautefeuille: Financial Interests, Personal, Advisory Board: AAA, Amgen, Servier, Pierre Fabre, Ipsen, Merck, Deciphera. A. Zaanan: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Merck Serono, Roche, Sanofi, Servier, Baxter, Bristol Myers Squibb, MSD, Pierre Fabre, Havas Life, Zymeworks, Daiichi Sankyo, AstraZeneca. R. Cohen: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Exeliom Biosciences, Enterome Biosciences; Financial Interests, Personal, Invited Speaker: Pierre Fabre, MSD Oncology, Servier; Financial Interests, Personal, Research Grant: Servier Institute. T. Lecomte: Financial Interests, Personal, Advisory Board: Sanofi, Amgen, Servier, Merck Serono, Ipsen, Bristol Myers Squibb, AstraZeneca, Pierre Fabre, Chugai Pharma. Y.H. Lam: Financial Interests, Personal, Advisory Role: Servier. S. Le Sourd: Financial Interests, Advisory Board: AstraZeneca, Servier, BTG, Pierre Fabre, Roche, Merck. C. Lepage: Financial Interests, Personal, Advisory Board: Amgen, AAA, Pierre Fabre, Ipsen. O. Bouche: Financial Interests, Personal, Advisory Board: Amgen, Merck, Apmonia Therapeutics, Deciphera; Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, Bayer. All other authors have declared no conflicts of interest.