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
143P - Ablation combined with tislelizumab in treating hepatocellular carcinoma: A phase II trial
Presenter: Yangxun Pan
Session: Poster Display
Resources:
Abstract
144P - Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer from K-MASTER project
Presenter: Jwa Hoon Kim
Session: Poster Display
Resources:
Abstract
145P - Tislelizumab (TIS) + chemotherapy (Chemo)/chemoradiotherapy (CRT) as neoadjuvant treatment for resectable esophageal squamous cell carcinoma (R-ESCC)
Presenter: Longqi Chen
Session: Poster Display
Resources:
Abstract
146P - Phase (ph) Ib results of bemarituzumab (BEMA) added to capecitabine/oxaliplatin (CAPOX) or S-1/oxaliplatin (SOX) with or without nivolumab (NIVO) for previously untreated advanced gastric/gastroesophageal junction cancer (G/GEJC): FORTITUDE-103 study
Presenter: Keun-Wook Lee
Session: Poster Display
Resources:
Abstract
147P - Four-year overall survival (OS) update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (uHCC)
Presenter: Stephen Chan
Session: Poster Display
Resources:
Abstract
148P - Safety and efficacy of atezolizumab (Atezo) + bevacizumab (Bev) in Japanese patients (pts) with unresectable hepatocellular carcinoma (uHCC): Preliminary analysis of a prospective, multicenter, observational study (ELIXIR)
Presenter: Teiji Kuzuya
Session: Poster Display
Resources:
Abstract
149P - A prospective observational study of MSI screening in unresectable chemotherapy-naïve advanced gastric cancer/gastroesophageal junction cancer: WJOG13320GPS
Presenter: Yukiya Narita
Session: Poster Display
Resources:
Abstract
150P - Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C
Presenter: Junwei Wu
Session: Poster Display
Resources:
Abstract
151P - Relationship between depth of response and early tumor shrinkage with overall survival in advanced pancreatic cancer
Presenter: EMIKA KUROKI
Session: Poster Display
Resources:
Abstract
152P - Interim analysis of the NAPOLEON-2 study: Safety evaluation of nanoliposomal irinotecan with fluorouracil and folinic acid for unresectable pancreatic cancer patients with prior biliary drainage
Presenter: Futa Koga
Session: Poster Display
Resources:
Abstract