Abstract 1289P
Background
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions occur in a range of tumour types. Larotrectinib, a central nervous system (CNS)-active and highly selective EMA- and FDA-approved TRK inhibitor, demonstrated an objective response rate (ORR) of 79% and a median duration of response (DoR) of 35.2 months across multiple cancers (Hong et al. Lancet Oncol 2020). We report updated data on patients with lung cancer treated with larotrectinib.
Methods
Patients with lung cancer harbouring an NTRK gene fusion enrolled in two clinical trials were pooled for this analysis. Larotrectinib 100 mg BID was administered on a continuous 28-day schedule. Response was assessed by the investigator per RECIST v1.1.
Results
As of 15 July 2019, 14 patients with metastatic TRK fusion lung cancer were enrolled: 13 with non-small cell lung cancer and 1 with small cell lung cancer. The median age was 52 years (range 25–76). Eleven patients had fusions involving NTRK1 and three patients had fusions involving NTRK3. Seven patients had baseline CNS metastases. Patients were heavily pre-treated with a median of three prior therapies (range 1–5); nine patients had received ≥2 prior therapies. The ORR with larotrectinib was 71% (95% CI 42–92%): one patient had a complete response, nine had partial responses, three had stable disease and one had progressive disease. The ORR in patients with CNS metastases was 57% (95% CI 18–90). The overall DoR ranged from 1.9+ to 28.7+ months. The median progression-free survival (PFS) had not been reached (range 1.8–30.3+ months), with an estimated PFS rate at 12 months of 69%. Treatment duration ranged from 2.1 to 39.6+ months. Larotrectinib was well tolerated, with treatment-emergent adverse events being mainly grade 1–2.
Conclusions
In this updated analysis, larotrectinib was shown to be highly active in patients with advanced lung cancer harbouring NTRK gene fusions, including those with CNS metastases. The drug has a favourable safety profile. These results support inclusion of NTRK gene fusions in routine molecular testing of patients with lung cancer.
Clinical trial identification
NCT02122913: First posted 25 April 2014; NCT02576431: First posted 15 October 2015.
Editorial acknowledgement
Editorial assistance was provided by Michael Sheldon PhD and Annabel Ola MSc (Scion, London, UK), funded by Bayer HealthCare Pharmaceuticals, Inc.
Legal entity responsible for the study
Bayer HealthCare Pharmaceuticals, Inc. and Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lily and Company.
Funding
Bayer HealthCare Pharmaceuticals, Inc. and Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lily and Company.
Disclosure
A. Drilon: Advisory/Consultancy: Loxo, Bayer, Lilly, Ignyta, Genentech, Roche, Takeda, Ariad, Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, AbbVie, 14ner/Elevation Onco; Honoraria (self): OncLive, PeerVoice, Research to Practice, Medscape, WebMD, Physicians Education Resources, Targeted Oncology; Advisory/Consultancy, Research grant/Funding (self): Foundation Medicine; Licensing/Royalties: Wolters Kluwer; Research grant/Funding (institution): GlaxoSmithKline, Teva, Taiho, PharmaMar; Travel/Accommodation/Expenses: Merck, Puma; Advisory/Consultancy, Research grant/Funding (institution): Pfizer, Exelixis; Non-remunerated activity/ies, Other: Merus, Boehringer Ingelheim. V. Moreno: Advisory/Consultancy, Educational grant: Medscape/Bayer. J. Patel: Advisory/Consultancy: ARIAD; Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Takeda Science Foundation. U.N. Lassen: Advisory/Consultancy: Bayer. B. Solomon: Travel/Accommodation/Expenses: AstraZeneca. L. Rosen: Research grant/Funding (self): Bayer. S. Leyvraz: Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer. D.S.W. Tan: Advisory/Consultancy: Merck; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self): BMS; Honoraria (self): Takeda; Research grant/Funding (self): Glaxosmithkline; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis. J.A. Reeves, L. Dima, N. Brega: Full/Part-time employment: Bayer. S. Kummar: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer. A.F. Farago: Research grant/Funding (self): PharmaMar, Ignyta, Amgen and Lilly; Advisory/Consultancy: Boehringer Ingelheim, Pfizer, and H3 Biomedicine; Advisory/Consultancy, Research grant/Funding (self): Bayer, Genentech, Roche, Bristol-Myers Squibb, AstraZeneca, AbbVie, Merck; Honoraria (self): Clinical Care Options, Medscape, Onclive, Research to Practice, and PeerView.