1300P - Treatment sequences in BRAF-V600-mutant non-small cell lung cancer: First-line targeted therapy versus first-line (chemo-) immunotherapy

Background

Targeted treatment with BRAF/MEK-inhibitors of patients with metastatic BRAF-V600-mutated (BRAFm) non-small-cell lung cancer (NSCLC) is effective but limited by acquired resistance. Patients with BRAFm NSCLC may derive long-lasting benefit from immune checkpoint inhibition with PD-1/-L1 antibodies (CPI). While CPI are the preferred first-line (1L) therapy in BRAFm melanoma, the optimal treatment sequence in BRAFm NSCLC is not defined.

Methods

Retrospective study of the clinical outcome of patients with metastatic BRAFm NSCLC diagnosed in the German national Network Genomic Medicine Lung Cancer (nNGM). Prespecified endpoints were overall survival (OS), time to treatment failure upon 1L palliative therapy (TTF1), and cumulative TTF of 1L and 2L therapy (cumulative TTF1+2).

Results

We identified 205 patients with BRAFm NSCLC (44% female, 97% adenocarcinoma, 70% smoker, 98.5% p.V600E). Median OS was 28.0 months, median TTF1 11.0 months. 175 patients received 1L therapy with dabrafenib/trametinib (DAB/TRM, n=114, 65%), CPI alone (n=34, 19%), or chemo-immunotherapy (n=27, 15%). There was no difference between 1L (chemo-) immunotherapy and DAB/TRM in OS (HR 0.92, p=0.7), TTF1 (HR 0.88, p=0.5), or cumulative TTF1+2. Overall, women had superior OS (HR 0.6, p=0.039, multivariate model), which was mainly driven by superior OS of female versus male patients receiving 1L DAB/TRM (OS HR 0.53, p=0.013). There was no gender difference in survival of patients receiving CPI-based 1L treatment (OS HR 1.04). Surprisingly, high PD-L1 status (TPS ≥50%) impacted negatively on TTF1 (HR 1.81, p=0.003, adjusted for sex, OS n.s.) regardless if the 1L regimen was targeted therapy or CPI-based.

Conclusions

Targeted or CPI-based 1L treatment of BRAFm NSCLC have similar outcomes. Gender and PD-L1 status may support decision making at the individual patient level.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Wiesweg: Financial Interests, Personal, Invited Speaker: Amgen, Roche, Takeda, GSK, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: GSK, Novartis, Pfizer, Roche, Janssen, Daiichi Sankyo, Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Takeda; Financial Interests, Institutional, Funding: Bristol Myers Squibb. F.C. Saalfeld: Financial Interests, Personal, Advisory Board: Janssen, Takeda, AstraZeneca, Janssen, BMS; Financial Interests, Personal, Invited Speaker: Pfizer, GWT TUD GmbH, AstraZeneca, Novartis, German Society for Thoracic Surgery; Financial Interests, Personal, Writing Engagement: Thieme; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Personal, Training: Lilly; Non-Financial Interests, Member: German Cancer Society - AIO. M. Hilbrandt: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. F. Griesinger: Financial Interests, Institutional, Research Funding: ASTRA, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens, Amgen, GSK, Daiichi Sankyo, Gilead; Financial Interests, Personal, Invited Speaker: ASTRA, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, AbbVie, Siemens, Tesaro/GSK, Amgen, Sanofi, Daiichi Sankyo, BeiGene, Gilead, Merck; Financial Interests, Personal, Advisory Board: ASTRA, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, AbbVie, Tesaro/GSK, Siemens, Tesaro, Amgen, Sanofi, Daiichi Sankyo, BeiGene, Gilead, Merck. C. Kropf-Sanchen: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, Art Tempi, BMS, Boehringer Ingelheim, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Regeneron, Roche, Sanofi, Streamed up, Takeda; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Other, Reporting from conferences as an expert: Onkowissen; Non-Financial Interests, Institutional, Local PI: AstraZeneca, Novartis. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi, GSK, Pfizer; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, BioNTech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Roche, Sanofi, GSK, Lilly; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Amgen, Boehringer-Ingelheim, BeiGene, Daiichi Sankyo, GSK, BMS, Lilly, MSD, Regeneron, Roche; Financial Interests, Institutional, Local PI: Pfizer Seagen. A. Stenzinger: Financial Interests, Personal, Advisory Board: Aignostics, AstraZeneca, Janssen, Bayer, Seattle Genetics, Pfizer, MSD, Eli Lilly, Illumina, Thermo Fisher, Amgen, Astellas, Agilent, Qlucore, QuiP, Sanofi; Financial Interests, Institutional, Advisory Board: BMS, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: Roche, Incyte, Servier; Financial Interests, Institutional, Research Grant: Bayer, Chugai, BMS, Incyte, MSD. M. Sebastian: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Novartis, Takeda, Lilly, BMS, MSD, Merck, Amgen, Pierre Fabre, Gilead, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Roche, GSK; Financial Interests, Institutional, Research Grant: AstraZeneca. M.H.H. Schuler: Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Janssen, Roche, GSK, MSD; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen, Novartis, Roche, Sanofi, Takeda, Tacalyx, MSD; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca, Janssen; Non-Financial Interests, Principal Investigator, Member, Study Steering Board: Janssen; Non-Financial Interests, Principal Investigator, Member, Study Steering Committee: Amgen. M. Wermke: Financial Interests, Personal, Advisory Board: Novartis, Boehringer Ingelheim, Bayer, Bristol Myers Squibb, ImCheck Therapeutics, Immatics, Pfizer, AstraZeneca, Tacalyx GmbH, Regeneron, Zymeworks, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim, Synlab GmbH, Janssen, EMD Merck Serono, GWT TUD GmbH, Amgen, Novartis; Financial Interests, Personal, Other, Member of DSMC: ISA Therapeutics; Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Personal, Other, Congress Travel Cost Support: AstraZeneca, EMD Merck Serono, Janssen, Boehringer Ingelheim, Immatics, Daiichi Sankyo, Iovance. N. Frost: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, BeiGene, BMS, Boehringer Ingelheim, Daiichi Sankyo, Janssen Oncology, Merck Serono, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Invited Speaker: Berlinchemie, Boehringer Ingelheim, Eli Lilly, MSD, Roche, Sanofi, Regeneron; Financial Interests, Personal and Institutional, Research Grant, ANTELOPE trial (NCT05689671): Roche; Non-Financial Interests, Leadership Role, Member of the steering board, section thoracic oncology: Working Group Medical Oncology within German Cancer Society (AIO). H. Kopp: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Roche, Pfizer, Takeda, Sanofi/Aventis, Lilly; Financial Interests, Personal, Advisory Board: MSD, Novartis, MSD, BMS, AstraZeneca; Financial Interests, Personal, Writing Engagement: Boehringer-Ingelheim. P. Christopoulos: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda, Roche, Daiichi Sankyo; Financial Interests, Personal, Writing Engagement: Gilead; Financial Interests, Personal, Invited Speaker: Thermo Fisher; Financial Interests, Institutional, Funding: AstraZeneca, Boehringer Ingelheim, Amgen, Novartis, Roche; Financial Interests, Personal, Funding: Takeda. M. Scheffler: Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Takeda, Pfizer, Roche, Sanofi-Aventis, BMS; Financial Interests, Personal, Advisory Board: Amgen, Boehringer Ingelheim, Roche, Novartis, Amgen, Takeda, Pfizer, Pfizer, AMGEN, Takeda, Amgen, Janssen, BMS, AstraZeneca, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Writing Engagement: Amgen; Financial Interests, Personal, Other, Travel support: AstraZeneca; Financial Interests, Institutional, Local PI: Dracen Pharmaceuticals; Financial Interests, Institutional, Coordinating PI: Amgen, Dracen, Siemens Healthineers; Financial Interests, Personal, Steering Committee Member: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, Patient advocacy: Zielgenau e. V., YesWeCan(cer); Non-Financial Interests, Principal Investigator, YouTube channel for patients: OncoEducation. All other authors have declared no conflicts of interest.