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

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.

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.

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).