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
122P - Distinct transcriptomic immune profiling and clinicopathological features of cribriform morphology in colorectal adenocarcinomas
Presenter: Abdelhakim Khellaf
Session: Poster Display
Resources:
Abstract
123P - Spatial molecular profiling identifies FGF20 upregulation on cancer-associated fibroblast and FGFR2-PI3K/Akt activation in tumor cells of sporadic early-onset colon cancer
Presenter: Dave Hoon
Session: Poster Display
Resources:
Abstract
124P - Characteristics, prognosis and therapeutic effects of non-V600 BRAF mutated colorectal cancer
Presenter: Lalida Arsa
Session: Poster Display
Resources:
Abstract
125P - Final results of APOLLON-11 and SOYUZ-APOLLON study: Multicentre prospective observational post-authorization study of bevacizumab biosimilar in patients with metastatic colorectal cancer in real-world practice
Presenter: Alexey Tryakin
Session: Poster Display
Resources:
Abstract
126P - From tumor height (TH) to tumor regression grade (TRG) in locally advanced rectal cancers (LARC) during total neadjuvant therapy (TNT): A retrospective analysis
Presenter: Valeria Pusceddu
Session: Poster Display
Resources:
Abstract
127P - A meta-analysis of efficacy and safety from head-to-head first-line (1L) trials of epidermal growth factor receptor inhibitors (EGFRIs) versus bevacizumab in combination with chemotherapy (CT) doublets in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) by sidedness
Presenter: Takayuki Yoshino
Session: Poster Display
Resources:
Abstract
128TiP - A phase II study of cadonilimab + FOLFOXIRI and bevacizumab as initial therapy for unresectable proficient mismatch repair/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC)
Presenter: Rongbo Lin
Session: Poster Display
Resources:
Abstract
140P - Prevalence of claudin-18 isoform 2 (CLDN18.2) positivity in locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mg/GEJ) adenocarcinoma in patients (pts) in the Asia region: Phase III SPOTLIGHT and GLOW studies
Presenter: Hoo Hwoei Fen Soo
Session: Poster Display
Resources:
Abstract
141P - Early phase trials outcomes in refractory upper GI cancers: A 10-year analysis from the SCRI UK phase I unit
Presenter: Antonella Cammarota
Session: Poster Display
Resources:
Abstract
142P - The survival impact of the addition of durvalumab to cisplatin/gemcitabine in advanced biliary tract cancer: A real-world, retrospective, multicentric study
Presenter: Silvia Foti
Session: Poster Display
Resources:
Abstract