Abstract 365P
Background
Current knowledge on biomarkers (BRAF V600E /RAS mutations) is mainly based on metastatic colorectal cancer (mCRC) patients with proficient mismatch repair (pMMR) tumors. It is uncertain whether these biomarkers have the same implications in deficient mismatch repair (dMMR) mCRC patients. Our aim is to provide insight on the value of Lynch syndrome, BRAFV600E and RAS mutation status and treatment regimens on survival in dMMR mCRC patients treated outside clinical trials.
Methods
This observational cohort study combined the national Dutch cohort, including almost all Dutch centers (2014-2019), and national French cohort, including 18 French centers (2007-2017). Clinical, molecular and survival data were collected in mCRC patients with dMMR tumors receiving chemotherapy ± targeted therapy. Multivariable Cox proportional hazard regression was used to analyze the prognostic value of BRAF V600E and RAS mutation status and Lynch syndrome on progression-free survival (PFS) and overall survival (OS). Inverse probability weighing was used to analyze impact of treatment regimens on survival.
Results
In our large real-world evidence cohort of 707 dMMR mCRC patients, 438 patients were treated with first-line systemic therapy. Mean age of first-line treated patients was 61.9 years and 40% had a proven/suspected Lynch syndrome. Most tumors were right-sided (74%) with synchronous metastases (62%). BRAF V600E and RAS mutations were observed in 42% and 33%, respectively. Median PFS and OS were 6.0 months and 19.3 months from start of first-line therapy. Multivariable regression analysis showed known clinical and pathological characteristics as predictors for OS and PFS, but not Lynch syndrome, mutation of BRAF V600E or RAS. In addition, there were no survival differences according to type of chemo- and targeted therapy used.
Conclusions
BRAFV600E and RAS mutation status are not associated with poor prognosis in dMMR mCRC patients, in contrast to pMMR mCRC patients. Our findings may aid in estimating prognosis and clinical decision-making in dMMR mCRC treated with chemotherapy and targeted therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
UMC Utrecht.
Funding
Has not received any funding.
Disclosure
M. Koopman: Financial Interests, Institutional, Advisory Board, advisory board and speaker: Pierre Fabre; Financial Interests, Institutional, Advisory Board: MSD, Bayer; Financial Interests, Institutional, Advisory Board, Advisory Board, speaker: Servier; Financial Interests, Institutional, Invited Speaker: Merck, BMS, Servier; Financial Interests, Institutional, Research Grant: Servier, Roche, Bayer, Bristol Myers Squibb, Merck, Personal Genomics Diagnostics, Sirtex, Pierre Fabre; Financial Interests, Institutional, Funding: Pierre Fabre, Amgen, Nordic Farma, Novartis, Merck, Servier, BMS; Non-Financial Interests, Leadership Role, vice-chair of DCCG: Dutch Colorectal Cancer Group; Non-Financial Interests, Advisory Role, Member of KWF scientific board: KWF; Non-Financial Interests, Other, ESMO faculty member for the Gastro-Intestinal Tumours – colorectal cancer: ESMO; Non-Financial Interests, Advisory Role, expert member of committee “regie op registers dure geneesmiddelen” ZINNL: ZiNNL; Non-Financial Interests, Advisory Role, CRC expert on Kanker.nl platform for answering online CRC questions of CRC (non) patients: Patient representative organisation (Kanker.nl); Non-Financial Interests, Leadership Role, chair of RWD & DH working group: ESMO; Other, Other, PI of the Dutch Prospective Colorectal Cancer Cohort study: PLCRC project. G. Vink: Financial Interests, Institutional, Research Grant: BMS, Merck, Servier, Personal Genome Diagnostics, Bayer, Sirtex, Pierre Fabre, Lilly. C.J.A. Punt: Financial Interests, Institutional, Advisory Board: Nordic Pharma. R. Cohen: Financial Interests, Institutional, Research Grant: Servier Institute, Nuovo-SoldatiFoundation, ARC Foundation for Cancer Research, MSD; Financial Interests, Institutional, Other, Honoraria: Servier, MSD Oncology. A. Zaanan: Financial Interests, Personal, Invited Speaker: Merck, Pierre Fabre; Financial Interests, Personal, Advisory Board: Baxter, Havas Life; Financial Interests, Personal, Principal Investigator: Amgen, Roche. D. Sefrioui: Financial Interests, Personal, Advisory Board: Servier, Ipsen; Financial Interests, Personal, Principal Investigator: Astellas; Financial Interests, Personal, Training: Roche. T. Lecomte: Financial Interests, Personal, Advisory Board: Amgen, Servier; Financial Interests, Personal, Invited Speaker: Sanofi; Non-Financial Interests, Personal, Other, Congress: Amgen. T. Aparicio: Financial Interests, Personal, Advisory Board: Sirtec; Financial Interests, Personal, Invited Speaker: Sanofi, Amgen; Non-Financial Interests, Personal, Other, Congress: Roche. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, BMS, Roche, Servier, Pierre Fabre. J. Roodhart: Financial Interests, Institutional, Research Grant: Bayer, BMS, Merck-Serono, Pierre Fabre, Servier, HUB 4 organoids, Cleara Biotech; Non-Financial Interests, Institutional, Advisory Board: ONCODE. All other authors have declared no conflicts of interest.