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Mini Oral session I

378 - Activity of larotrectinib in TRK fusion lung cancer

Date

11 Apr 2019

Session

Mini Oral session I

Presenters

Alexander Drilon

Citation

Annals of Oncology (2019) 30 (suppl_2): ii38-ii68. 10.1093/annonc/mdz063

Authors

A. Drilon1, S. Kummar2, V. Moreno3, J. Patel4, U. Lassen5, L. Rosen6, B.H. Childs7, S. Nanda7, M.C. Cox8, N.C. Ku8, A.F. Farago9

Author affiliations

  • 1 Memorial Sloan Kettering Cancer Center, 10017 - New York/US
  • 2 Stanford Cancer Institute, Stanford/US
  • 3 Start Madrid-fjd, Hospital Fundación Jiménez Díaz, Madrid/ES
  • 4 University of Chicago, Chicago/US
  • 5 Department Of Oncology, Rigshospitalet, Copenhagen/DK
  • 6 UCLA, Los Angeles/US
  • 7 Bayer Healthcare Pharmaceuticals, Whippany/US
  • 8 Loxo Oncology, South San Francisco/US
  • 9 Cancer Center, Massachusetts General Hospital, Boston/US
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Resources

Abstract 378

Background

Tropomyosin receptor kinases (TRK) fusions involving NTRK1, NTRK2 and NTRK3 genes occur in a diverse range of tumor types including lung cancer. Larotrectinib, the first FDA-approved selective TRK inhibitor, has demonstrated an overall response rate of 75% by independent central review across a broad range of tumor types (Drilon et al., NEJM 378:731-9, 2018). Here we report on the subset of lung cancer patients that have been treated with larotrectinib.

Methods

NSCLC patients with TRK fusion cancer detected by molecular profiling from two clinical trials (NCT02122913 and NCT02576431) were eligible. Larotrectinib (100 mg BID) was administered on a continuous 28-day schedule until withdrawal, unacceptable toxicity or disease progression. Efficacy was investigator assessed using RECIST version 1.1.

Results

As of July 30, 2018 eleven patients with metastatic lung adenocarcinoma were enrolled. Median age was 52 years (range 25 – 76). Eight patients had fusions involving NTRK1 and diverse fusion partners; EPS15 (n = 2), TPM3 (n = 2), IRF2BP2 (n = 2), TPR (n = 1), SQSTM1 (n = 1). Three patients had fusions involving NTRK3; fusion partners SQSTM1 (n = 2) and ETV6. Ten patients had prior systemic therapy (5 patients had 3 or more prior therapies) with best response on last prior therapy being 1 partial response and 4 stable disease. Seven patients were evaluable for response to larotrectinib. One patient had a complete response, 4 patients had a partial response, and 2 patients had stable disease (ORR 71%). The median time to response was 1.8 months. The duration of response ranged from 7.4+ months to 17.6+ months; the median duration of response was not reached. Two patients discontinued treatment due to disease progression and 1 withdrew consent. Four patients were on treatment less than 1 month and were non-evaluable for efficacy. Larotrectinib was well tolerated, with treatment related adverse events being predominantly grade 1 and grade 2.

Conclusions

Larotrectinib is highly active in lung cancer patients harboring NTRK gene fusions. These results strongly support the inclusion of NTRK gene fusions as part of routine molecular testing for patients with lung cancer.

Clinical trial identification

NCT02122913, NCT02576431.

Editorial acknowledgement

Legal entity responsible for the study

Loxo Oncology Inc. Bayer AG.

Funding

Loxo Oncology Inc. Bayer AG.

Disclosure

A. Drilon: Honoraria: Ignyta, Loxo, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Genentech, Roche, Takeda, ARIAD, Millenium, Helsinn, Beigene, BerGenBio, Hengrui Therapeutics, Exelixis, Bayer, Tyra Biosciences; Research: Foundation Medicine. V. Moreno: Educational grant: Medscape/Bayer. U. Lassen: Honorarium: Bayer. L. Rosen: Research funding: Loxo Oncology. B.H. Childs, S. Nanda: Employee: Bayer Healthcare Pharmaceuticals. M.C. Cox, N.C. Ku: Employee: Loxo Oncology. A.F. Farago: Consulting: Bayer; Consulting, research funding: Loxo, AstraZeneca, Genentech, Pharmamar, AbbVie & Stemcentrx; Research funding: Ignyta, Merck, BMS. All other authors have declared no conflicts of interest.

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