559P - Comprehensive survey of AACR GENIE database revealed a wide range of TMB distribution among all three classes (I, II, III) of BRAF mutated NSCLC

Background

BRAF mutated Non-Small Cell Lung Cancer (NSCLC) can be divided into three classes. Only class I (BRAF V600E/X) mutated NSCLC has FDA approved treatment options. The other two classes due to their unique mechanisms of oncogenesis do not have approved treatment. We explored any potential molecular differences between these three classes focused primarily on tumor mutation burden (TMB) to assess if immune checkpoint inhibitors (ICIs) is a possible option for all three classes of BRAF+ NSCLC.

Methods

We queried the public AACR GENIE database (version 13.1) that included TMB as performed by the AACR GENIC database.

Results

Out of 20,713 unique NSCLC patients, 3.96% were either class I, II, or III BRAF mutations (class I: 1.6%, class II: 1.3%; class III: 1.1%). An additional 1.7% non-class I-III BRAF mutations were identified but were not analyzed for this abstract. The mean age, sex, racial composition, and distribution of the BRAF mutations in all three classes are shown in the table. The median TMB (mt/MB) were 6.5, 9.5, and 10.3 for class I, II, and III BRAF+ NSCLC respectively. 30.5 % of V600E had TMB ≥ 10; 47.7% of class II had TMB ≥ 10; and 52.5% of class III had TMB ≥ 10. For those patients with TMB ≥ 10, the median TMB was 45, 28.9, 18.4 for class I, II, and III respectively with a 7.7% with range of median TMB between 50-100 (class I), 10.4% with median TMB range 100-500 (class II), 8.1% with median TMB range of 100-500 (class III). There is no statistical significance in the mean or median TMB by pair-wise comparison of all three classes. Genomic co-alterations were being analyzed and will be updated. Table: 559P

Conclusions

BRAF+ NSCLC patients are elderly. Class III has the highest median TMB followed by class II then class I. Based on TMB distribution, there is extensive heterogeneity within each three classes of BRAF+ NSCLC. Many BRAF+ NSCLC tumors have a high proportion having TMB ≥ 10. ICI is a potential treatment option for substantial proportion of all three classes of BRAF+ NSCLC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Nagasaka: Financial Interests, Personal, Advisory Board: AstraZeneca, Caris Life Sciences, Daiichi Sankyo, Novartis, EMD Serono, Janssen, Lilly, Pfizer, Genentech, Mirati, Regeneron, Silverback; Financial Interests, Personal, Invited Speaker: Takeda, Blueprint; Financial Interests, Personal, Other, Travel: AnHeart. S.I. Ou: Financial Interests, Personal, Invited Speaker: Pfizer, Roche; Financial Interests, Personal, Advisory Board: JNJ/Janssen, Elevation Oncology, AnHeart Therapeutics; Financial Interests, Personal, Ownership Interest: MBrace Therapeutics, BlossomHill Therapeutics; Financial Interests, Institutional, Local PI: Pfizer, Mirati, JNJ/Janssen, Merus, Revolution Medicine, Nuvalent. All other authors have declared no conflicts of interest.