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.