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ePoster Display

100P - Characteristics and outcomes of patients (pts) with NTRK fusion-positive (NTRK+) metastatic / locally advanced (LA) solid tumours receiving non-TRK inhibitor (TRKi) standard of care (SoC), and prognostic value of NTRK fusions in clinical practice

Date

16 Sep 2021

Session

ePoster Display

Presenters

George Demetri

Citation

Annals of Oncology (2021) 32 (suppl_5): S382-S406. 10.1016/annonc/annonc686

Authors

G.D. Demetri1, S. Peters2, D.P. Hibbar3, J. Davies4, S.L. Maund5, L. Veronese6, H. Liu7, O. Humblet8, L. Perez9

Author affiliations

  • 1 Department Of Medical Oncology/sarcoma/ludwig Center, Dana Farber Cancer Institute and Ludwig Center, Harvard Medical School, 02215 - Boston/US
  • 2 Centre Hospitalier Universitarie Vaudois (chuv), Lausanne University Hospital, 1011 - Lausanne/CH
  • 3 Personalized Healthcare Analytics, Genentech, Inc., South San Francisco/US
  • 4 Personalized Healthcare Data Science, Roche Products Ltd, Welwyn Garden City/GB
  • 5 Oncology Biomarker Development, Genentech, Inc., South San Francisco/US
  • 6 Medical Oncology, F. Hoffmann-La Roche Ltd, Basel/CH
  • 7 Product Development Oncology, Genentech, Inc., South San Francisco/US
  • 8 Quantitative Sciences, Flatiron Health Inc., New York/US
  • 9 Personalized Healthcare Data Science, F. Hoffmann-La Roche Ltd, Basel/CH
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Abstract 100P

Background

NTRK fusions are actionable biomarkers with efficient and well tolerated TRKis. Clinical profile and outcomes of pts with NTRK+ tumours receiving non-TRKi SoC are unknown and the prognosis of NTRK+ pts vs pts with NTRK fusion-negative (NTRK–) tumours is not well known.

Methods

Demographic and clinical data for TRKi-naïve adults with metastatic/LA solid tumours and ≥1 Foundation Medicine NGS test (1 Jan 2011 – 31 Dec 2019) were extracted from a US electronic health record-derived clinicogenomic database (CGDB; Flatiron Health). NTRK– pts from the CGDB were matched 10:1 to NTRK+ pts based on cancer type and propensity score with preselected prognostic variables (age; smoking status; practice type; lines of therapy from initial diagnosis to NGS report; stage at diagnosis; time from metastatic/LA diagnosis to NGS report; co-mutations). Overall survival (OS), defined as time from index date (metastatic/LA stage diagnosis or start of last treatment) to death/censoring, was compared between NTRK+ and matched NTRK– cohorts. NTRK fusion prognostic value was evaluated via univariate Cox proportional hazard model.

Results

Of 58001 CGDB pts with solid tumours, 28 had NTRK+ metastatic/LA cancers. NTRK+ pts tended to be younger, with less history of smoking, more brain metastases and a shorter time from advanced diagnosis to first NGS report vs all NTRK– pts; no differences were significant (Table). Median (95% CI) OS was 10.2 months (7.2–14.1) in NTRK+ pts vs 10.4 months (6.7–14.3) in matched NTRK– pts (n=280); hazard ratio (HR; 95% CI) for death was 1.6 (1.0–2.5). Results were similar using start of last treatment as index (HR 1.6; 1.0–2.5). Table: 100P

% of pts All NTRK- pts (n=24903) Matched NTRK- pts (n=280) NTRK+ pts (n=28)
Age ≥65 years 49.6 43.9 39.3
History of smoking No 40.5 54.6 57.1
ECOG PS 0–1 / 2–4 / Unknown 49.7 / 12.1 / 38.1 N/A* 50.0 / 7.1 / 42.9
Practice type Academic / Community 11.4 / 88.6 18.9 / 81.1 14.3 / 85.7
Lines of therapy from diagnosis to NGS report 0–2 / ≥3 / Unknown 68.0 / 19.4 / 12.6 70.0 / 10.4 / 19.6 71.4 / 10.7 / 17.9
Stage at initial diagnosis 0–II / III–IV / Unknown 17.8 / 72.0 / 10.2 16.8 / 66.8 / 16.4 17.9 / 64.3 / 17.9
Brain metastases Yes / No or Unknown 10.6 / 89.4 N/A* 17.9 / 82.1
Metastatic/advanced diagnosis to NGS report Mean (SD), days 272.10 (446.92) 158.95 (371.16) 151.21 (245.20)

*ECOG PS and brain metastases not matched due to high % unknown

Conclusions

In this small cohort of TRKi-naïve pts, OS was similarly poor in pts with NTRK+ metastatic/LA cancers vs matched NTRK– pts; this contrasts with improved OS in pts with NTRK+ tumours who receive TRKi therapy.

Clinical trial identification

Editorial acknowledgement

Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Laura Vergoz, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

G.D. Demetri: Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Ignyta; Financial Interests, Personal, Advisory Role: Ikena Therapeutics; Financial Interests, Personal, Advisory Role: Genentech, Inc.; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: EMD-Serono; Financial Interests, Personal, Advisory Role: Loxo Oncology; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: WCG/Arsenal Capital; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Merrimack Pharmaceuticals; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Epizyme; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Mirati; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Icon PLC; Financial Interests, Personal, Advisory Role: Ziopharm; Financial Interests, Personal, Advisory Role: Polaris Pharmaceuticals; Financial Interests, Personal, Advisory Role: Medscape; Financial Interests, Personal, Advisory Role: Relay Therapeutics; Financial Interests, Personal, Advisory Role: CellCarta; Financial Interests, Personal, Advisory Role: McCann Health; Financial Interests, Institutional, Funding: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Funding: Ignyta; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Loxo Oncology; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Epizyme; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Personal, Stocks/Shares: Blueprint Medicines; Financial Interests, Personal, Stocks/Shares: G1 Therapeutics; Financial Interests, Personal, Stocks/Shares: Ikena Therapeutics; Financial Interests, Personal, Stocks/Shares: Caris Life Sciences; Financial Interests, Personal, Stocks/Shares: Bessor Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Erasca Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Champions Oncology; Financial Interests, Personal, Stocks/Shares: Translate Bio; Financial Interests, Personal, Stocks/Shares: Relay Therapeutics; Financial Interests, Personal, Stocks/Shares: CellCarta; Financial Interests, Institutional, Licensing Fees: Novartis; Financial Interests, Personal, Member of the Board of Directors: Blueprint Medicines; Financial Interests, Personal, Member of the Board of Directors: Translate BIO; Non-Financial Interests, Personal, Other, Non-renumerated activities: Alexandria Real Estate Equities; Financial Interests, Personal, Other, Honoraria: M.J. Hennessey/OncLive; Financial Interests, Personal, Other, Honoraria: AACR/ASCO; Financial Interests, Personal, Other, Travel, accomodation, expenses: Epizyme; Financial Interests, Personal, Other, Travel, accomodation, expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Honoraria: Medscape. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody; Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda; Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, Pfizer, Phosplatin Therapeutics. D.P. Hibbar, S.L. Maund, H. Liu: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc. J. Davies: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. L. Veronese, L. Perez: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. O. Humblet: Financial Interests, Personal, Full or part-time Employment: Flatiron Health Inc.

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