Abstract 1686P
Background
BRAF mutations can be classified into 3 groups based on molecular characteristics. Targeted therapies exist for Class 1 (V600) BRAF mutations, but effective treatments have not been established for non-V600 Class 2 or 3 BRAF mutations. Several clinical trials are enrolling patients with Class 2/3 mutations, but many barriers to enrollment persist. We sought to determine whether BRAF mutation class varied according to key demographic differences in cancer populations.
Methods
Using the AACR GENIE (v11.1) cancer database, we analyzed the incidence and distribution of BRAF mutation class in cancer patients according to: sex, age, primary race, and tumor type. Pediatric patients and those with missing information on sex and age were excluded. The chi-square test and multivariate probit regression models were used to evaluate significant differences between groups.
Results
BRAF mutations were identified in 6558 (5.4%) samples among 121,221. Of these, 5857 were classified as Class 1, 2, or 3. The most frequent cancer types were melanoma (30%), colorectal cancer (CRC, 21%), and non-small cell lung cancer (NSCLC, 13%). Median age was 63 years old. Across all cancer types, we observed significant differences in the distribution of mutations by class, according to patient sex, age, and primary race. These demographic variables were independently associated with BRAF class in multivariable analyses. Similar trends were observed within cancer types, including melanoma, NSCLC, and CRC (Table). Table: 1686P
Patient characteristics according to BRAF mutation class
| BRAF class 1 (n=3830) | BRAF class 2 (n=1205) | BRAF class 3 (n=822) | p-value | |
| Sex | ||||
| Female | 2006 (67.5%) | 591 (19.9%) | 373 (12.5%) | <0.0001 |
| Male | 1824 (63.1%) | 614 (21.3%) | 449 (15.6%) | |
| Age | ||||
| <60 | 1692 (70.3%) | 414 (17.2%) | 301 (12.5%) | <0.0001 |
| 60+ | 2138 (63.2%) | 791 (22.9%) | 531 (15.1%) | |
| Primary race | ||||
| White | 3035 (65.4%) | 952 (20.5%) | 657 (14.1%) | <0.0001 |
| Asian | 139 (60.2%) | 55 (23.8%) | 37 (16.0%) | |
| Black | 104 (48.4%) | 65 (30.2%) | 46 (21.4%) |
Conclusions
Our analysis reveals that older, male, Black and Asian patients are more likely to have Class 2/3 BRAF mutations compared to younger, female and White patients. More research is needed to determine the molecular mechanisms governing these associations. Our results highlight the need to address disparities in access to next generation sequencing and to clinical trial enrollment so that patients with actionable Class 2/3 BRAF mutations can receive novel targeted therapies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Canadian Cancer Society.
Disclosure
A. Rose: Financial Interests, Institutional, Funding: Immediate Family Member employed by Merck, Canadian Cancer Society, Canadian Institutes of Health Research, Jewish General HospitalFoundation, TransMedTech Institute. All other authors have declared no conflicts of interest.