1301P - BRAF-mutant metastatic non-small cell lung cancer: Real-world data from the Italian biomarker ATLAS database

Background

BRAF mutations identify a small subgroup of non-small cell lung cancer (NSCLC) patients (pts). Dabrafenib/trametinib (D/T) combination is associated with high response rates and durable anti-tumor activity in BRAF-V600-mutants, albeit the optimal sequence with immunotherapy-based therapies and the efficacy in pts with brain metastases (BMs) remain unclear. Here we report outcomes among advanced BRAF-mutant NSCLC pts from the Italian ATLAS registry.

Methods

Retrospective data were collected and analyzed using ATLAS, a web-based platform created to collect and share NSCLC data among Italian centers.

Results

244 BRAF-mutated NSCLC pts diagnosed from 2019 to 2023 in 18 Italian centers were enrolled, including 70% of V600E mutations, 27.5% non-V600E mutations and 2.5% non-otherwise specified BRAF mutations. D/T was used as 1^stline therapy in 55.3% of the pts, as 2^nd and 3^rd line in 6.6% and 0.8%, respectively. Median progression-free survival (mPFS) of first line D/T was 19.8 months (mos) (95% CI: 10.3-29.3), with a 2-year (2-yr) overall survival (OS) rate of 64.9% and a PFS2 of 6.6 mos (95% CI: 0-14.3). Non-targeted 1^st line treatment was associated with 12 mos mPFS (95% CI: 4.3-19.7) and 77.1% 2-yr OS rate. Among 66 pts treated with 2^nd line therapy, mPFS was not reached with D/T (1-yr PFS rate: 69.3%) as compared with 10.5 mos with other treatments. 2-yr OS rates were 100% with D/T and 45.9% with other treatments, respectively. Among pts with BMs (11.8%), 1^st line D/T was associated with a 9.2 mos mPFS (95% CI: 0.8-17.6) and 2-yr OS rate of 49.5%. The activity of D/T differs among selected subgroups, including sex (mPFS 13.6 mos vs 25.3 mos, 2-yr OS rate 54.9% vs 72.3% in males and females, respectively) and smoking status (mPFS 18.4 mos vs 25.6 mos vs 24 mos in never, former and current smokers, respectively).

Conclusions

These data confirm the efficacy of D/T in BRAF V600E mutant NSCLC patients in a real-world setting, with a sustained activity in treatment-naïve pts, including those with BMs. The clinical impact of immunotherapy w/o chemotherapy in BRAF-mutants as first or subsequent line in different PD-L1 level and molecular subgroups remains to be defined.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Russo: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Pfizer, Roche, Takeda, Amgen. E. Bria: Financial Interests, Personal, Advisory Board: AZ, Roche, BMS, MSD, Eli Lilly, Pfizer, Novartis, Takeda; Financial Interests, Personal, Invited Speaker: AZ, Roche, BMS, MSD, Eli Lilly, Pfizer, Novartis, Takeda; Financial Interests, Institutional, Research Grant: AZ, Roche. S. Grisanti: Financial Interests, Personal, Advisory Board: Roche, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol-Myers; Financial Interests, Institutional, Funding: Roche, AstraZeneca. S. Novello: Financial Interests, Personal, Invited Speaker: AZ, MSD, Eli Lilly, Novartis, BeiGene, Amgen, Thermo Fisher; Financial Interests, Personal, Advisory Board: BI, BMS, Pfizer, Takeda, Roche, Sanofi, Amgen, J&J; Financial Interests, Institutional, Coordinating PI, IIT: MSD, BI; Financial Interests, Institutional, Coordinating PI: AZ, AMG, Eli Lilly, Sanofi, J&J, Roche; Non-Financial Interests, Leadership Role, president of this European advocacy: WALCE; Non-Financial Interests, Member: IASLC, AIOM, ASCO. All other authors have declared no conflicts of interest.