1299P - First-line immunotherapy versus BRAF and MEK inhibitors for patients with BRAF V600E mutant metastatic non-small cell lung cancer

Background

Although targeted therapy (TT) with BRAF + MEK inhibitors is highly effective in BRAF V600E mutant non-small cell lung cancer (NSCLC), these patients (pts) can also derive durable benefit from immune checkpoint inhibitors +/- chemotherapy (ICI±CT). Whether TT should be always prioritized over ICI±CT as first-line (1L) therapy in this population is unknown.

Methods

Clinicopathologic and outcomes data were collected from pts with metastatic NSCLC treated with 1L ICI±CT or TT between 2015 and 2024 at 6 centers in EU and US.

Results

Of 111 pts, 35 received 1L ICI±CT and 76 received 1L TT. Pts who received ICI±CT, compared to pts who received TT, were younger (median age 65 vs 71.5 y, P=0.04) and more likely to have a history of tobacco use (82.9% vs 56%, P=0.01). There was no difference in sex, histology, ECOG PS, PD-L1 TPS, number of metastatic sites, and median follow-up time. Median overall survival (mOS) to ICI±CT was 43.3 months (mo) vs 23.3 mo to TT (HR 0.69, P=0.20). OS rates at 1, 2, and 3 years were 72%, 59%, and 55% with ICI±CT vs 75%, 50%, and 40% with TT. After adjusting for confounders, 1L ICI±CT vs TT was associated with improved OS (HR 0.49, P=0.04) in multivariable analysis. In examining key subgroups, longer mOS with ICI±CT vs TT was noted in heavy smokers (≥30 pack-years) (HR 0.26, P=0.03) and females (HR 0.40, P=0.04), but not in never/light smokers (HR 1.06, P=0.86) or males (HR 1.19, P=0.66). No OS difference was noted between ICI±CT vs TT in pts with (HR 1.14, P=0.80) or without brain metastasis (HR 0.57, P=0.13) nor with PD-L1 ≥50% (HR 0.57, P=0.19) or <50% (HR 1.34, P=0.52). The response rate (ORR) to ICI±CT was higher in pts who received ICI±CT as 1L compared to pts who received ICI±CT as 2^nd line (2L) after 1L TT (55% vs 19%, P<0.01), while the ORR to TT was similar between pts who received TT as 1L and pts who received TT as 2L after 1L ICI±CT (64% vs 50%, P=0.24). Pts who received TT as 1L, compared to pts who received TT as 2L after 1L ICI±CT, had similar adverse events of any grade (74% vs 71%, P=0.82) or grade ≥3 (23% vs 24%, P=0.94).

Conclusions

Individual clinical factors should be used to tailor 1L therapy in pts with BRAF V600E mutant NSCLC. Additional analyses to better define the optimal therapeutic sequence in this population will be conducted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Di Federico: Non-Financial Interests, Personal, Advisory Board: Hanson-Wade. M.F. Chen: Financial Interests, Personal, Research Funding: T32-CA009207; Financial Interests, Personal and Institutional, Research Funding: ASCO Young Investigator Award; Financial Interests, Personal, Stocks/Shares: Nordisk, Quest, Doximity, Figs. F.R. Ogliari: Non-Financial Interests, Institutional, Coordinating PI: MSD, Roche, BMS, Daiichi Sankyo, BeiGene. M. Grant: Financial Interests, Personal, Research Funding: Adela; Financial Interests, Other, Honoraria: Regeneron, Daiichi Sankyo, AstraZeneca. J.V. Alessi: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, Janssen. F. Gelsomino: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, BMS, Eli Lilly. M.V. Negrao: Financial Interests, Personal, Advisory Board: Mirati, Merck/MSD, Novartis, Genentech, Sanofi; Other, Personal, Funding: Ziopharm Oncology, ApotheCom, Ashfield Healthcare; Non-Financial Interests, Personal, Research Funding: Mirati, Novartis, Checkmate, Alaunos, AstraZeneca, Pfizer, Genentech, Navire. R. Ferrara: Financial Interests, Personal, Advisory Board: MSD, BeiGene. M. Awad: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Pfizer, BMS, Foundation Medicine, Novartis, Gritstone Bio, Mirati Therapeutics, EMD Serono, AstraZeneca, Instil Bio, Regeneron, Janssen, Addini-T Therapeutics; Financial Interests, Institutional, Research Funding: Genentech/Roche, Lilly, AstraZeneca, BMS, Amgen; Financial Interests, Personal, Sponsor/Funding: BMS. G.J. Riely: Financial Interests, Institutional, Research Funding: Novartis, Roche/Genentech, Mirati therapeutics, Merck, Takeda, Lilly, Pfizer, Rain Therapeutics; Financial Interests, Institutional, Royalties, Patent application submitted covering pulsatile use of erlotinib to treat or prevent brain metastases (Inst): Patent; Financial Interests, Personal, Sponsor/Funding: Bayer, Merck; Other, Personal, Other: Pfizer, Roche/Genentech, Takeda, Mirati Therapeutics. A. Ardizzoni: Financial Interests, Personal and Institutional, Research Grant: Celgene, BMS, Ipsen, Roche; Financial Interests, Personal, Advisory Board: BMS, Merck, Roche, AstraZeneca, Eli Lilly. D. Planchard: Financial Interests, Personal, Speaker, Consultant, Advisor: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Daiichi Sankyo, F. Hoffman-La Roche, Janssen, Merck, Novartis, Pfizer, Samsung. M.D. Offin: Financial Interests, Personal, Other, Honoraria: OncLive; Financial Interests, Personal, Speaker, Consultant, Advisor: PharmaMar, Novartis, Targeted Oncology, Jazz Pharmaceuticals, American Society for Radiation Oncology, Pfizer; Financial Interests, Personal, Sponsor/Funding: BMS, Merck Shar & Dohme; Non-Financial Interests, Personal, Non remunerated activity: Mesothelioma Applied Research Foundation. B.E. Johnson: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Checkpoint Therapeutics, AstraZeneca, Daiichi Sankyo, GSK, Genentech, Bluedot Bio, G1 Therapeutics, Jazz Pharmaceuticals, Merus, Abdera, Simcere Pharmaceutical; Non-Financial Interests, Personal, Steering Committee Member: Pfizer. B. Ricciuti: Financial Interests, Personal, Advisory Board: Regeneron, AstraZeneca, Amgen; Financial Interests, Personal, Sponsor/Funding: Regeneron, Genentech, BMS; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Targeted Oncology. All other authors have declared no conflicts of interest.