Abstract 447P
Background
BRAF mutations (BRAFm) in colorectal cancer (CRC) are seen in 8% of late stage and 15% of early stage disease. In metastatic CRC, BRAFm is prognostic for poor overall survival. The clinical significance of BRAFm in early stage disease has been described as a poor prognostic factor, however there is heterogeneity seen within this population. We aim to assess prognostic variables in a cohort of BRAFm CRC.
Methods
We retrospectively collected clinical characteristic and outcome data from patients diagnosed with BRAFm early stage CRC at the Royal Marsden Hospital from March 2014 to December 2020. Next generation sequencing of the BRAF gene was performed as part of routine care. Variables including gender, age at diagnosis, stage of disease, side of primary, MMR status and type of BRAF mutation were assessed and survival estimates calculated. Analyses were performed using Cox regression.
Results
There were 166 patients with BRAFm early stage CRC, including 75 (45.2%) males. Median age at diagnosis was 69 years. 4 (2.4%) patients had stage 1 disease, 53 (31.9%) stage 2 disease, 105 (63.3%) stage 3 disease, and 4 without staging (2.4%). 123 (74%) primary tumours were right sided, 42 (25%) left sided and 1 unknown. 85 (51.2%) of tumours were dMMR, 73 (44%) pMMR tumours, 8 (4.8%) were unknown. 158 had V600E mutations, 8 were non-V600E. 111 patients were relapse free at 4 years. There was a significant difference in 4 year relapse free survival (RFS) between pMMR tumours (37%) compared with dMMR tumours (84%) (HR 4.43, p<0.01). Those with node positive disease had an almost 3 times higher risk of relapse compared to node negative disease (p=0.003). Left sided tumours were also more likely to relapse compared to right sided (HR 1.94, p=0.02). There was no significant difference between V600E and non-V600E tumours on RFS. In a multi-variate analysis, nodal stage (HR 3.37, p=0.01) and pMMR status was associated with the highest risk of relapse (HR 4.68, p<0.001).
Conclusions
In early stage BRAFm CRC, MMR status and nodal stage of disease was predictive of relapse in our real world cohort.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Royal Marsden NHS Foundation Trust.
Funding
Royal Marsden NHS Foundation Trust.
Disclosure
S. Rao: Financial Interests, Personal, Advisory Board: Bayer; Roche; Financial Interests, Personal, Other, Travel and accommodation: Incyte; Bayer. D. Cunningham: Financial Interests, Institutional, Research Grant: AstraZeneca; Clovis; Eli Lilly; 4SC; Bayer; Celgene; NIHR EME; Leap; Roche; Financial Interests, Personal, Advisory Board: OVIBIO. I. Chau: Financial Interests, Personal, Advisory Board: Astella; Astra-Zeneca; Bayer; Boehinger Ingelheim; BMS; Eisai; Eli Lilly; Incyte; Merck; MSD; OncXerna; Pierre Fabre; Roche; Financial Interests, Personal, Invited Speaker: Eli Lilly; Other, Personal, Other, DMC Chairman: Five Prime Therapeutics; Financial Interests, Institutional, Principal Investigator: Cilag-Janssen; Eli Lilly. N. Starling: Financial Interests, Personal and Institutional, Research Grant, + Travel grant: AstraZeneca; BMS; Financial Interests, Institutional, Research Grant: Pfizer; NIHR EME; Financial Interests, Personal, Funding, Travel grant + Honoraria: Eli Lilly; Merck; MSD Oncology; Financial Interests, Personal, Funding, Travel grant: Roche; Financial Interests, Personal, Other, Honoraria: Pierre Fabre; Servier; GSK; Amgen; Financial Interests, Personal, Advisory Board: Pfizer; AstraZeneca; Servier; Merck. All other authors have declared no conflicts of interest.