1394P - Real-world experience in treatment of patients with non-small cell lung cancer with BRAF and cMET Exon 14 skipping mutations

Background

BRAF and cMET Exon 14 skipping are rare mutations of NSCLC. Opposite to other alterations, the preferred treatment sequencing in 1^st and 2^nd line is not clear.

Methods

We created an international registry for patients (pts) with advanced NSCLC harboring BRAF and cMET exon 14 skipping mutations, diagnosed from Jan 2017 until June 2022, excluding pts enrolled in clinical trials. Clinicopathologic and molecular data were collected, and treatment patterns were recorded. Clinical endpoints according to treatment assignment were assessed using Kaplan-Meier curves and Cox regression models.

Results

Data on 58 pts from 7 centers across 5 countries were included in the final analysis. Forty patients had cMET exon 14 skipping mutation and 18 had BRAF V600E mutation. Main characteristics: median age 66.7 (range: 36.0-91.0) years, female sex (48.0%), never or past smokers (71.0%), performance status 0-1 in (84.0%), adenocarcinoma (86.2%), stage IIIC - IV at diagnosis (82.2%), bone and brain metastasis (45.0%, and 21.0%, respectively). Mutations were uniformly diagnosed by NGS in all centers. Programmed death-ligand 1 TPS was <1% in 18%, 1-49% in 34% and >50% in 48% of cases. Fifty-three and 28 pts received 1^st and 2^nd line treatments, respectively, among which 52.8% received targeted therapy (TT) in 1^st line and 53.5% in 2^nd line. Overall response rate (ORR) and disease control rate (DCR) for 1^st line treatment with TT vs. other (IO +/- CT ) was 55.6% vs. 21.7% (p = 0.0084) and 66.7% vs 39.1% (p = 0.04), respectively. Type of treatment in 1^st line (TT vs. IO +/- CT) affected Time to Treatment Discontinuation (TTD), 11.6 m vs. 4.6 m, p = 0.006. Overall survival for the whole group was 15.4 m and was not statistically influenced by the type of treatment (19.2 m vs. 13.5 m; p = 0.83).

Conclusions

This real-world retrospective study suggests that TT in the 1^st line is the preferred option for the treatment of pts with advanced NSCLC with BRAF and cMET exon 14 skipping mutations, as opposed to IO +/- CT, due to higher ORR and DCR, longer TTD and the fact that almost half of the patients did not receive 2^nd line treatment. U Janzic and W. Shalata contributed equally to this study.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

U. Janzic: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Roche, Pfizer; Financial Interests, Personal and Institutional, Advisory Board: MSD, BMS, Takeda, Amgen, Boehringer Ingelheim; Financial Interests, Institutional, Other: Novartis. W. Shalata, A. Agbarya, R. Dziadziuszko, M. Jakopovic: Financial Interests, Personal and Institutional, Advisory Board: Roche, AstraZeneca, MSD, Pfizer, Novartis, BMS. K. Szymczak: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, Novartis, BMS, Amgen, Vipharm. G. Mountzios: Financial Interests, Personal and Institutional, Advisory Board: Roche, AstraZeneca, MSD, BMS, Gilead, Pfizer, Boehringer Ingelheim, Novartis, Amgen, Mirati, Bioatlas. A. Pluzanski: Financial Interests, Personal and Institutional, Advisory Board: BMS, MSD, AstraZeneca, Roche.