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ePoster Display

535P - Larotrectinib efficacy and safety in adult patients with tropomyosin receptor kinase (TRK) fusion cancer

Date

16 Sep 2021

Session

ePoster Display

Presenters

Marcia S. Brose

Citation

Annals of Oncology (2021) 32 (suppl_5): S583-S620. 10.1016/annonc/annonc699

Authors

M.S. Brose1, L. Shen2, D.S.W. Tan3, S. Kummar4, J.J. Lin5, R. McDermott6, J. Berlin7, M. Tahara8, U.N. Lassen9, S. Leyvraz10, J.D. Patel11, R. Norenberg12, L. Dima13, N. Brega14, D.S. Hong15, A. Drilon16

Author affiliations

  • 1 Otorhinolaryngology: Head And Neck Surgery, Abramson Cancer Center of the University of Pennsylvania School of Medicine, 19106 - Philadelphia/US
  • 2 Department Of Gi Oncology, Peking University Cancer Hospital & Institute, Beijing/CN
  • 3 Division Of Medical Oncology, National Cancer Centre Singapore, Singapore/SG
  • 4 Department Of Medicine, Stanford Cancer Center, Stanford University, Palo Alto/US
  • 5 Department Of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston/US
  • 6 Oncology (medical Oncology), St Vincent's University Hospital and Cancer Trials Ireland, Dublin/IE
  • 7 Division Of Hematology/oncology, Vanderbilt University Medical Center, Nashville/US
  • 8 Head And Neck Medical Oncology Dept., National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 9 Department Of Oncology, Rigshospitalet, Copenhagen/DK
  • 10 Charité Comprehensive Cancer Center, Charité – Universitätsmedizin Berlin, Berlin/DE
  • 11 Lurie Cancer Center/department Of Medicine, Northwestern University, Chicago/US
  • 12 Chrestos Institut, Chrestos Concept GmbH & Co. KG, Essen/DE
  • 13 Global Oncology, Bayer HealthCare Pharmaceuticals, Inc., Basel/CH
  • 14 Sbu Oncology, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 15 Department Of Investigational Cancer Therapeutics, 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, New York/US
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Abstract 535P

Background

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions have been identified as oncogenic drivers in various tumour types. Larotrectinib is a first-in-class, highly selective, central nervous system (CNS)-active TRK inhibitor approved for the treatment of adult and paediatric patients (pts) with TRK fusion cancer, with a 78% objective response rate (ORR) and 36.8-month median progression-free survival (PFS) across multiple non-CNS cancers (McDermott et al, ESMO 2020). We report an updated analysis of the efficacy and safety of larotrectinib in adult pts with TRK fusion cancer.

Methods

Adults (≥18 years [y]) with non-CNS TRK fusion cancer treated in 3 larotrectinib clinical trials were included in this analysis. The primary endpoint was investigator-assessed ORR (RECIST v1.1). Data cut-off: 20 July 2020.

Results

A total of 140 adult pts across 20 tumour types were included in this analysis (130 pts evaluable for efficacy). Median age was 55 y (range 19–84 y). Pts had received a median of 2 systemic therapies (range 0–10). ORR was 67% (95% CI 58–75): 12% complete responses; 55% partial responses (3 pts pending confirmation); 20% stable disease; 9% progressive disease; and 4% not determined. ORR in 15 evaluable pts with baseline CNS metastases was 73% (95% CI 45–92). Across all patients, the median duration of response was 49.3 months (95% CI 26.3–not estimable) at a median follow-up of 23.2 months. Median PFS was 25.8 months (95% CI 12.7–51.1) at a median follow-up of 22.1 months. Although median overall survival (OS) had not been reached at a median follow-up of 24.0 months, the 36-month OS rate was 66% (95% CI 56–77). Duration of treatment ranged from 0.03+ to 60.4+ months. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 17 pts (12%). One pt discontinued due to a TRAE. There were no new safety signals.

Conclusions

In this updated analysis with longer follow-up, larotrectinib continues to demonstrate robust and durable tumour-agnostic efficacy with extended survival benefits in adults with TRK fusion cancer, including those with CNS metastases. Larotrectinib also has a favourable safety profile. These data reinforce the use of routine NTRK gene fusion testing in pts with solid tumours.

Clinical trial identification

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

Editorial acknowledgement

Medical writing assistance was provided by Farzana Miah, MSc, of Scion Medica, London, UK.

Legal entity responsible for the study

Bayer and Loxo Oncology (a subsidiary of Lilly).

Funding

Bayer and Loxo Oncology (a subsidiary of Lilly).

Disclosure

M.S. Brose: Financial Interests, Institutional, Research Grant, Research Support: Bayer, Loxo Oncology, Genentech, Eisai, Blueprint Medicines, Lilly and Novartis; Financial Interests, Personal, Advisory Role, Consulting: Bayer, Loxo Oncology, Genentech, AstraZeneca, and Lilly; Financial Interests, Institutional, Other, Honoraria: Clinical Care Options, Medscape, OncLive and PeerView. L. Shen: Financial Interests, Institutional, Funding, Funding grants: Beijing Xiantong Biomedical Technology Co., Ltd, Qilu Pharmaceutical Co., Ltd, Zaiding Pharmaceutical (Shanghai) Co., Ltd, Jacobio Pharmaceuticals Co., Ltd., Beihai Kangcheng(Beijing)Medical Technology Co.,Ltd.; Financial Interests, Personal, Advisory Role, Consulting: MSD, Merk, BI, Harbour; Financial Interests, Personal, Invited Speaker, Speaker fee: Hutchison Whampoa, Hengrui, ZaiLab, CStone. D.S.W. Tan: Financial Interests, Personal, Advisory Role, Consulting: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer; Financial Interests, Institutional, Other, Travel: Pfizer, Boehringer Ingelheim, Roche; Financial Interests, Institutional, Other, Honoraria: BMS, Takeda, Novartis, Roche, Pfizer; Financial Interests, Institutional, Research Grant, Research funding: Novartis, GSK, AstraZeneca. S. Kummar: Financial Interests, Personal, Full or part-time Employment, Editor-in-Chief of Current Problems in Cancer: Elsevier; Financial Interests, Personal, Other, Consulting: Boehringer Ingelheim, Springworks Therapeutics, Varian, Bayer, Genome & Company, HarbourBiomed, Mundibiopharma, Seagen,; Financial Interests, Institutional, Advisory Board: Bayer, Genome & Company, HarbourBiomed, Gilead; Financial Interests, Personal, Other, Travel: Bayer; Financial Interests, Personal, Full or part-time Employment, Co-founder/equity: PathomIQ; Financial Interests, Personal, Other, Spouse advisor/founder: Cadila Pharmaceutical ltd., Arxeon Inc.. J.J. Lin: Financial Interests, Personal, Other, Personal Fees/Other: Pfizer, Genentech, C4 Therapeutics, Nuvalent, Blueprint Medicines, Turning Point Therapeutics, Hengrui Therapeutics, Neon Therapeutics, Relay Therapeutics, Novartis, Bayer, Elevation Oncology, Roche. R. McDermott: Financial Interests, Personal, Other, Travel: Janssen-Cilag, Pfizer; Financial Interests, Institutional, Other, Honoraria: Bayer, Sanofi, Janssen, Astellas, BMS, MSD, Pfizer, Novartis, Clovis; Financial Interests, Institutional, Research Grant, Funding: Sanofi, Janssen, Bayer, Astellas. J. Berlin: Financial Interests, Institutional, Research Grant, Funding: Bayer; Financial Interests, Institutional, Advisory Board: Bayer. M. Tahara: Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Bayer, Merck Serono, MSD Ono Pharmaceutica, Rakuten Medical, Pfizer, Lilly, AstraZeneca, LOXO; Financial Interests, Institutional, Other, Honoraria: Eisai, MSD, Ono Pharmaceutica, Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant, Funding: Bayer, Ono Pharmaceutica. U.N. Lassen: Financial Interests, Institutional, Advisory Board: Bayer, Pfizer, Novartis; Financial Interests, Institutional, Research Grant, Funding: BMS, GSK, Pfizer and Roche. S. Leyvraz: Financial Interests, Institutional, Advisory Role: Bayer; Financial Interests, Institutional, Other, Travel: Bayer. J.D. Patel: Financial Interests, Personal, Advisory Role, Consulting: ARIAD, Abbvie, AstraZeneca and Takeda Science Foundation. R. Norenberg: Financial Interests, Personal, Full or part-time Employment, External employee: Bayer; Financial Interests, Personal, Full or part-time Employment: Contract research organization (CRO). L. Dima: Financial Interests, Personal, Full or part-time Employment: Bayer. N. Brega: Financial Interests, Personal, Full or part-time Employment: Bayer. D.S. Hong: Financial Interests, Institutional, Research Grant, Funding: 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, Pfize; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Loxo Oncology, MiRNA, ASCO, AACR, SITC, Genmab; Financial Interests, Personal, Advisory Role, Consulting: Alpha Insights, Axiom, Adaptimmune, Baxter, Bayer, Genentech, GLG, Group H, Guidepoint Global, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Seattle Genetics, Takeda, and Trieza Therapeutics; Financial Interests, Personal, Ownership Interest, Advisor/founder: Molecular Match, OncoResponse, Presagia Inc.A. Drilon: Financial Interests, Personal, Advisory Role, Honoraria/advisory boards: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millennium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, Abbvie, 14ner/Elevation Onc; Financial Interests, Institutional, Research Grant, Associated research paid to institution: Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, PharmaMar; Financial Interests, Institutional, Research Grant: Foundation Medicine; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, Food/Beverage: Merck, Puma, Merus, Boehringer Ingelheim; Financial Interests, Institutional, Other, CME Honoraria: Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, Axis, Peerview Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Medscape, Clinical Care Optio.

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