Abstract 559P
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
Class I (N = 324) | Class II (N = 260) | Class III (N = 236) | |
Mean age (SD) | 67.4+/-10.5 | 69.0+/-8.9 | 67.6+/-9.6 |
Sex (%) | Female (58.6%) | Female (56.5%) | Female (49.6%) |
Race | White (70.7%)Black (8.3%)Asian (4.9%)Unknown (16%) | White (80.4%)Black (6.9%)Asian (2.3%)Unknown (10.4%) | White (77.5%)Black (10.6%)Asian (2.1%)Unknown (9.7%) |
Mutations | V600E (99.1%) V600K (0.6%) V600D (0.3%) | G469A/V/R (64.6%) K601E/N (23.5%) G464V/E (9.6%) L597Q (2.6%) | G466V/E/A (39.0%) D594N/G/A/H (29.2%) N581S/I (20.3%) G596R (8.5%) G469E (1.7%) V459L (0.85%) D287H (0.4%) S467L (0.4%) |
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.
Resources from the same session
62P - Combination of chemotherapy with endocrinal therapy as upfront treatment of metastatic breast cancer in hormone receptor- positive, HER2 -negative disease: A phase II randomised clinical trial
Presenter: Mariam Saleh
Session: Poster Display
Resources:
Abstract
63P - Efficacy and safety of eribulin plus carboplatin combination for HER2-negative metastatic breast cancer
Presenter: Mengqian Ni
Session: Poster Display
Resources:
Abstract
64P - Unmet needs following metastatic breast cancer in a middle-income Asian country
Presenter: Nirmala Bhoo-Pathy
Session: Poster Display
Resources:
Abstract
66P - Utidelone-based therapy in metastatic solid tumors after failure of standard therapies: A prospective, multicenter, single-arm trial
Presenter: Jianjun Zhang
Session: Poster Display
Resources:
Abstract
67P - Efficacy and safety of trastuzumab biosimilar in HER2+ve metastatic breast cancer: A multicenter phase III study
Presenter: krishna Mohan
Session: Poster Display
Resources:
Abstract
68P - Neratinib in combination with fulvestrant and or palbociclib can overcome endocrine resistance in HER2-low/ ER+ breast cancer
Presenter: Maryam Arshad
Session: Poster Display
Resources:
Abstract
69P - A multicenter, retrospective, real-world study of inetetamab combined with pyrotinib and vinorelbine as treatment for HER2-positive metastatic breast cancer
Presenter: Nan Jin
Session: Poster Display
Resources:
Abstract
70P - Overall survival of eribulin, trastuzumab, and pertuzumab as first-line therapy for patients with HER2-positive metastatic breast cancer: A phase II, single-arm clinical trial
Presenter: Kenichi Inoue
Session: Poster Display
Resources:
Abstract
71P - Efficacy and safety of disitamab vedotin after trastuzumab for HER2 -positive breast cancer: A real-world data of retrospective study
Presenter: Chao Li
Session: Poster Display
Resources:
Abstract
72P - Real-world data on the efficacy of T-DM1 biosimilar for the treatment of HER2-positive metastatic breast cancer patients: Outcomes from a single center retrospective study in India
Presenter: Kaushal Patel
Session: Poster Display
Resources:
Abstract