Abstract 667P
Background
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers of various tumour types, including salivary gland tumours (SGTs). Secretory carcinoma of the salivary gland, a rare subset of SGTs, is characterised by an ETV6-NTRK3 gene fusion found in ≥80% of cases. Larotrectinib is a highly selective, central nervous system-active, tropomyosin receptor kinase (TRK) inhibitor with an objective response rate (ORR) of 92% across 24 evaluable patients (pts) with a variety of SGTs, as of July 2020 (Le et al. Oncologist 2022 [in press]). We report updated efficacy and safety of larotrectinib in pts with TRK fusion SGTs with longer follow-up.
Methods
Pts with TRK fusion SGTs were identified from two larotrectinib clinical trials (NCT02122913, NCT02576431). Pts received larotrectinib 100 mg twice a day (BID) except for one pt who received 150 mg BID in the phase 1 trial (NCT02122913). Response was assessed by independent review committee (per Response Evaluation Criteria in Solid Tumours v1.1).
Results
As of July 2021, 25 pts with TRK fusion SGTs were identified, including 24 with an additional year of follow-up. Median age was 59.0 years (range 28–80). All pts had ETV6-NTRK3 gene fusions. ORR was 84% (95% CI 64–95%): 8 complete responses, 13 partial responses, 2 stable disease and 2 progressive disease. Median time to response was 1.8 months. Median duration of response (DoR) was not reached; median follow-up was 39.6 months. Median progression-free survival (PFS) was 56.0 months (95% CI 30.8–not estimable) at a median follow-up of 41.3 months. Median overall survival (OS) was not reached at a median follow-up of 43.7 months. The 36-month DoR, PFS, and OS rates were 71%, 64%, and 82%. Duration of treatment ranged from 1.0 to 68.0 months. At data cut-off, 8 pts had progressed, with 5 pts continuing treatment post-progression for ≥4 weeks. Treatment-related adverse events (TRAEs) were mostly Grade 1–2. Grade 3–4 TRAEs were reported in 6 pts (24%). There were no treatment discontinuations due to TRAEs.
Conclusions
Larotrectinib demonstrated rapid and durable efficacy with a favourable safety profile in pts with TRK fusion SGTs. These data highlight the importance of identifying NTRK gene fusions in pts with SGTs.
Clinical trial identification
NCT02122913, NCT02576431.
Editorial acknowledgement
Medical writing assistance was provided by Anastasija Pesevska, PharmD, of Scion Medica, London, UK.
Legal entity responsible for the study
The authors.
Funding
These studies were funded by Bayer HealthCare Pharmaceuticals, Inc. and Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company.
Disclosure
D.S. Hong: Financial Interests, Institutional, Research Grant: AbbVie, Adaptimmune, Amgen, AstraZeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa, Lilly, Loxo Oncology, Merck, MedImmune, Mirati, MiRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer; Financial Interests, Personal, Other, travel/accommodation/expenses: Loxo Oncology, MiRNA, ASCO, AACR, SITC, Genmab; Financial Interests, Personal, Advisory Role: Alpha Insights, Axiom, Adaptimmune, Baxter, Bayer, Genentech, GLG, Group H, Guidepoint Global, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, Trieza Therapeutics; Financial Interests, Personal, Ownership Interest: Molecular Match (advisor), OncoResponse (founder), and Presagia Inc (advisor). M. Tahara: Financial Interests, Personal, Advisory Role: Bayer, Merck Serono, MSD Ono Pharmaceutica, Rakuten Medical, Pfizer, Lilly, AstraZeneca, Loxo; Financial Interests, Personal, Other, Honoraria: Eisai, MSD, Ono Pharmaceutica, Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Bayer, Ono Pharmaceutica. C. Baik: Financial Interests, Institutional, Research Grant: AbbVie, Lilly, AstraZeneca, Janssen, Spectrum, Pfizer, Blueprint, Turning Point, Daiichi Sankyo, Loxo Oncology; Financial Interests, Advisory Role: AstraZeneca, Blueprint, Daiichi Sankyo, Takeda, Turning Point, Guardant. J.R. Bauman: Financial Interests, Personal, Advisory Role: Pfizer, Bayer, Kura, Janssen, Blueprint Medicine, Merck, BeiGene, and Turning Point, AstraZeneca, Lilly; Financial Interests, Institutional, Research Grant: BMS. J. Gilbert: Financial Interests, Personal, Advisory Role: Cue Pharmaceutical; Financial Interests, Institutional, Other, payments to institution for participation in clinical trials: Pfizer, BMS, Amgen, and Exelexis. M.S. Brose: Financial Interests, Institutional, Research Grant: Bayer, Loxo Oncology, Genentech, Eisai, Blueprint Medicines, Lilly and Novartis; Financial Interests, Personal, Advisory Role: Bayer, Loxo Oncology, Genentech, AstraZeneca, and Lilly; Financial Interests, Personal, Other, Honoraria: Clinical Care Options, Medscape, OncLive and PeerView. J.E. Grilley-Olson: Financial Interests, Personal, Advisory Role: SpringWorks and Sorrento. T. Patil: Financial Interests, Personal, Other, Honoraria: Roche/Genentech, AstraZeneca, PRIME Oncology, and Aptitude Health, Llc; Financial Interests, Personal, Advisory Role: Guidepoint and Axiom. R. McDermott: Financial Interests, Personal, Advisory Board: Amgen, Bayer, BMS, Clovis, Janssen, Pfizer; Financial Interests, Personal, Invited Speaker: Astellas, Ipsen, MSD; Financial Interests, Personal, Principal Investigator: Astellas, Bayer, BMS, Clovis, Regeneron, MSD. L.E. Raez: Financial Interests, Institutional, Research Grant: Loxo, BMS, Pfizer, AstraZeneca, Syndax, Mirati, Nanth Health, Liquid Genomics, Guardant Health, Lilly Oncology, Merck. J.M. Johnson: Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Merck; Financial Interests, Personal, Advisory Role: Foundation Medicine and Rakuten. L. Shen: Financial Interests, Institutional, Funding: Beijing Xiantong Biomedical Technology Co., Ltd, Qilu Pharmaceutical Co., Ltd., Zaiding Pharmaceutical (Shanghai) Co., Ltd, Yaojie Ankang (Nanjing) Technology Co., Ltd., Baiji Shenzhou (Beijing) Biotechnology Co., Ltd.; Financial Interests, Personal, Advisory Role: MSD, BMS, Merck, AstraZeneca, Daiichi Sankyo, Roche, Minji Biopharmaceutical, Harbour BioMed; Financial Interests, Personal, Speaker’s Bureau: Hutchison Whampoa, MSD. R. Norenberg: Financial Interests, Personal, Full or part-time Employment: Bayer. L. Dima: Financial Interests, Personal, Full or part-time Employment: Bayer. C. Mussi: Financial Interests, Personal, Full or part-time Employment: Bayer. X. Le: Financial Interests, Personal, Advisory Role: EMD Serono (Merck KGaA), AstraZeneca, Spectrum Pharmaceutics, Boehringer Ingelheim, AbbVie, Novartis, Janssen, Hengrui Therapeutics, Daiichi Sankyo, and Eli Lilly; Financial Interests, Institutional, Research Grant: Eli Lilly and Boehringer Ingelheim. A.E. Drilon: Financial Interests, Personal, Advisory Board: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, AbbVie, 14ner/Elevation Onco; Financial Interests, Institutional, Research Grant: Pfizer, Exelixis, GSK, Teva, Taiho, PharmaMar; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other: Merck, Puma, Merus, Boehringer Ingelheim; Financial Interests, Personal, Other, CME honoraria: Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, Axis, Peerview Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, AXIS, EPG Health, JNCC/Harborside.