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E-Poster Display

1955P - Survival benefits of larotrectinib in an integrated dataset of patients with TRK fusion cancer

Date

17 Sep 2020

Session

E-Poster Display

Presenters

Raymond McDermott

Citation

Annals of Oncology (2020) 31 (suppl_4): S1034-S1051. 10.1016/annonc/annonc294

Authors

R. McDermott1, C.M. van Tilburg2, A.F. Farago3, S. Kummar4, D.S.W. Tan5, C.M. Albert6, J. Berlin7, U.N. Lassen8, F. Doz9, B. Geoerger10, L. Mascarenhas11, N. Federman12, J.A. Reeves13, L. Dima13, N. Brega13, E. De La Cuesta13, T.W. Laetsch14, D.S. Hong15, A. Drilon16

Author affiliations

  • 1 Medical Oncology, St Vincents University Hospital, D04 T6F4 - Dublin/IE
  • 2 Department Of Pediatric Oncology, Hematology, Immunology And Pulmonology, Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Research Center (DKFZ), Heidelberg/DE
  • 3 Cancer Center, Massachusetts General Hospital, Boston/US
  • 4 Stanford Cancer Institute, Stanford University, 94305 - Stanford/US
  • 5 Division Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 6 Pediatric Hematology & Oncology, Seattle Children’s Hospital and University of Washington School of Medicine, Seattle/US
  • 7 Department Of Hematology/oncology, Vanderbilt University Medical Center, Nashville/US
  • 8 Department Of Oncology, Rigshospitalet, 2100 - Copenhagen/DK
  • 9 Oncology Center Siredo Care Innovation Research For Children, Adolescents And Young Adults With Cancer, Institut Curie and University of Paris, Paris/FR
  • 10 Department Of Pediatric And Adolescent Oncology, Gustave Roussy Cancer Center, Université Paris-Saclay, Paris/FR
  • 11 Division Of Hematology And Oncology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles/US
  • 12 Departments Of Pediatrics And Orthopaedics, David Geffen School of Medicine, University of California, Los Angeles/US
  • 13 Oncology, Bayer HealthCare Pharmaceuticals, Inc., Whippany/US
  • 14 Department Of Pediatrics, University of Texas Southwestern Medical Center/Children’s Health, Dallas/US
  • 15 Division Of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston/US
  • 16 Early Drug Development Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 10065 - New York/US
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Abstract 1955P

Background

Larotrectinib is a first-in-class, CNS-active, EMA- and FDA-approved selective tropomyosin receptor kinase (TRK) inhibitor. TRK proteins are encoded by the NTRK genes; gene fusions involving NTRK are rare oncogenic drivers seen in a range of paediatric and adult tumour types. Pooled analysis of three clinical trials showed that larotrectinib induced an investigator-assessed overall response rate (ORR) of 79%, median progression-free survival (PFS) of 28.3 months (95% CI 22.1–NE) and median overall survival (OS) of 44.4 months (95% 36.5–NE) in 159 patients (pts) with TRK fusion cancer (Hong et al, Lancet Oncol. 2020). Here we report updated survival data with longer follow-up in an integrated dataset of 175 pts with TRK fusion cancer treated with larotrectinib.

Methods

Data were pooled from three clinical trials of pts with non-primary CNS TRK fusion cancer treated with larotrectinib. Disease status was assessed by investigators using RECIST v1.1. Primary endpoint was ORR and secondary endpoints included PFS, OS, duration of response (DoR) and safety outcomes. Data cut-off: 15 July 2019.

Results

A total of 175 pts were included in the integrated dataset. The median age was 43 y (range 0.1–84.0). The ORR was 78% (95% CI 71–84): 19% complete response, 59% partial response, 13% stable disease and 7% progressive disease. Median DoR was not estimable (NE) at a median follow-up of 13.5 months, with a 12-month DoR rate of 81% (95% CI 73–89). At a median follow-up of 13.8 months, median PFS was 36.8 months (95% CI 25.7–NE), showing extended benefit compared to previous analysis. Although median OS had not been reached with a median follow-up of 15.3 months, the 12-month OS rate was 90% (95% CI 85–95). Larotrectinib-related adverse events (AEs) were mainly Grade 1/2 with no new safety signals identified; two pts discontinued due to larotrectinib-related AEs.

Conclusions

These data confirm that treatment with larotrectinib offers extended survival benefit in pts with TRK fusion cancer. Larotrectinib continued to demonstrate a favourable long-term safety profile. Screening pts for NTRK gene fusions should be actively considered.

Clinical trial identification

NCT02122913, first posted April 25, 2014; NCT02637687, first posted 22 December 2015; NCT02576431: first posted 15 October 2015.

Editorial acknowledgement

Editorial assistance was provided by Farzana Miah, MSc, 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

R. McDermott: Travel/Accommodation/Expenses: Janssen-Cilag; Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Bayer; Honoraria (self): Sanofi; Honoraria (self): Janssen; Honoraria (self): Astellas; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Clovis; Research grant/Funding (self): Sanofi; Research grant/Funding (self): Janssen; Research grant/Funding (self): Bayer; Research grant/Funding (self): Astellas. C.M. van Tilburg: Advisory/Consultancy: Bayer; Advisory/Consultancy: Novartis. A.F. Farago: Advisory/Consultancy, Research grant/Funding (self): Bayer; Research grant/Funding (self): Loxo Oncology; Advisory/Consultancy, Research grant/Funding (self): Genentech; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): AbbVie; Research grant/Funding (self): PharmaMar; Advisory/Consultancy, Research grant/Funding (self): Merck; Research grant/Funding (self): Ignyta; Research grant/Funding (self): Amgen ; Research grant/Funding (self): Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: H3 Biomedicine; Honoraria (self): Clinical Care Options; Honoraria (self): Medscape; Honoraria (self): Onclive; Honoraria (self): Research to Practice; Honoraria (self): PeerView. S. Kummar: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer. D.S.W. Tan: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Merck; Advisory/Consultancy: Loxo; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self): BMS; Honoraria (self): Takeda; Research grant/Funding (self): GSK. J. Berlin: Advisory/Consultancy, Research grant/Funding (self): Bayer. U.N. Lassen: Advisory/Consultancy: Bayer. F. Doz: Advisory/Consultancy, Travel/Accommodation/Expenses, All honoraria contributed to a research account at Institut Curie, not to his personal funds: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses, All honoraria contributed to a research account at Institut Curie, not to his personal funds: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses, All honoraria contributed to a research account at Institut Curie, not to his personal funds: Roche; Advisory/Consultancy, All honoraria contributed to a research account at Institut Curie, not to his personal funds: Celgene; Advisory/Consultancy, All honoraria contributed to a research account at Institut Curie, not to his personal funds: Loxo Oncology; Advisory/Consultancy, All honoraria contributed to a research account at Institut Curie, not to his personal funds: Tesaro; Advisory/Consultancy, All honoraria contributed to a research account at Institut Curie, not to his personal funds: Servier. L. Mascarenhas: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Research grant/Funding (institution), All honoraria contributed to his research institution CHLA : Lilly; Advisory/Consultancy, Research grant/Funding (institution), All honoraria contributed to his research institution CHLA : Salarius; Research grant/Funding (institution), All honoraria contributed to his research institution CHLA: Pfizer; Research grant/Funding (institution), All honoraria contributed to his research institution CHLA: Loxo; Research grant/Funding (institution), All honoraria contributed to his research institution CHLA: AstraZeneca; Research grant/Funding (institution), All honoraria contributed to his research institution CHLA: Merck; Research grant/Funding (institution), All honoraria contributed to his research institution CHLA: Novartis; Research grant/Funding (institution), All honoraria contributed to his research institution CHLA: Amgen. N. Federman: Shareholder/Stockholder/Stock options, Stock held in for-profit healthcare companies: Genmab; Shareholder/Stockholder/Stock options, Stock held in for-profit healthcare companies: Reata pharmaceuticals; Shareholder/Stockholder/Stock options, Stock held in for-profit healthcare companies: BlueBird Bio; Advisory/Consultancy: Zelda Pharmaceuticals; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Licensing/Royalties: NanoValent Ltd. J.A. Reeves: Full/Part-time employment: Bayer. L. Dima: Full/Part-time employment: Bayer. N. Brega: Full/Part-time employment: Bayer. E. De La Cuesta: Full/Part-time employment: Bayer. T.W. Laetsch: Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy, Research grant/Funding (self): Loxo; Advisory/Consultancy, Research grant/Funding (self): Lilly; Advisory/Consultancy: Cellectis; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Abbvie; Research grant/Funding (self): Amgen; Research grant/Funding (self): Atara; Research grant/Funding (self): Biotherapeutics; Research grant/Funding (self): BMS; Research grant/Funding (self): Epizyme; Research grant/Funding (self): GSK; Research grant/Funding (self): Janssen; Research grant/Funding (self): Jubilant Pharmaceuticals; Research grant/Funding (self): Novella Clinical; Research grant/Funding (self): Servier. D.S. Hong: Research grant/Funding (self): AbbVie, Amgen, AstraZeneca, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Ignyta, Infinity, Kite, Kyowa, Lilly, Merck, MedImmune, Mirati, Molecular Templates, Mologen, NCI-CTEP, Novartis; Advisory/Consultancy, Research grant/Funding (self): Adaptimmune; Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy, Research grant/Funding (self): Genentech; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (self): Takeda; Research grant/Funding (self), Travel/Accommodation/Expenses: Loxo Oncology; Research grant/Funding (self), Travel/Accommodation/Expenses: MiRNA; Research grant/Funding (self), Travel/Accommodation/Expenses: Genmab; Travel/Accommodation/Expenses: ASCO, AACR, SITC; Advisory/Consultancy: Alpha Insights; Advisory/Consultancy: Axiom; Advisory/Consultancy: Baxter; Advisory/Consultancy: GLG; Advisory/Consultancy: Group H; Advisory/Consultancy: Guidepoint Global; Advisory/Consultancy: Infinity; Advisory/Consultancy: Janssen; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Medscape; Advisory/Consultancy: Numab; Advisory/Consultancy: Trieza Therapeutics; Shareholder/Stockholder/Stock options, ownership interests in Molecular Match (advisor), OncoResponse (founder), and Presagia Inc (advisor): Molecular Match; Shareholder/Stockholder/Stock options, ownership interests in Molecular Match (advisor), OncoResponse (founder), and Presagia Inc (advisor): OncoResponse ; Shareholder/Stockholder/Stock options, ownership interests in Molecular Match (advisor), OncoResponse (founder), and Presagia Inc (advisor): Presagia Inc. A. Drilon: Honoraria (self), Advisory/Consultancy: Verastem; Honoraria (self), Advisory/Consultancy: Tyra Biosciences; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Honoraria (self), Advisory/Consultancy: Hengrui Therapeutics; Honoraria (self), Advisory/Consultancy: BergenBio; Honoraria (self), Advisory/Consultancy: Beigene; Honoraria (self), Advisory/Consultancy: Helsinn; Honoraria (self), Advisory/Consultancy: Blueprint Medicines; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: TP Therapeutics; Honoraria (self), Advisory/Consultancy: Loxo Oncology, Bayer, Lilly, Takeda, Ariad, Millenium; Honoraria (self), Advisory/Consultancy: Ignyta/Genentech/Roche; Honoraria (self), Advisory/Consultancy: MORE Health; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Foundation Medicine; Licensing/Royalties: Wolters Kluwer; Travel/Accommodation/Expenses, food/beverages: Merck; Travel/Accommodation/Expenses, food/beverages: Puma Biotechnology; Honoraria (self), CME: Medscape; Honoraria (self), CME: OncLive; Honoraria (self), CME: PeerVoice; Honoraria (self), CME: Research to Practice; Honoraria (self), CME: Physicians Education Resources; Honoraria (self), CME: Targeted Oncology. All other authors have declared no conflicts of interest.

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