Abstract 366P
Background
TRK fusions are oncogenic drivers of a variety of tumors, many of which can involve the central nervous system (CNS). Larotrectinib is an FDA-approved selective TRK inhibitor for the treatment of TRK fusion cancer (Drilon et al., NEJM 2018). Here we report on the clinical activity of larotrectinib in an expanded set of TRK fusion-positive primary CNS tumors.
Methods
Patients with primary CNS tumors harboring an NTRK gene fusion detected by local molecular testing who were treated with larotrectinib in two clinical trials (NCT02637687 and NCT02576431) were identified. Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was investigator assessed (RANO). Data cutoff: February 19, 2019.
Results
18 patients with various histological types of glial tumors (11 high grade, 4 low grade, 3 unknown) were identified. The patients had gene fusions involving NTRK2 (n = 13), NTRK1 (n = 3) and NTRK3 (n = 2). Median age was 10.5 years (range 1.3–79.0); 14 patients were pediatric (< 18). In 14 evaluable patients, the objective response rate was 36% (2 CR [pending confirmation], 3 PR), with responses seen in high- and low-grade disease and across histologies. Nine patients had SD. The 24-week disease control rate was 71%. The duration of treatment ranged from 0.03+ to 16.6+ months.
Conclusions
Larotrectinib is active in patients with TRK fusion cancer with intracranial disease. Objective responses and durable disease control were seen in primary CNS tumors of various grades and histologies. These results further support expanded testing for NTRK gene fusions in patients with primary CNS tumors.
Clinical trial identification
NCT02637687 and NCT02576431.
Editorial acknowledgement
Legal entity responsible for the study
Bayer.
Funding
Bayer.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
371P - Clinical utility of Encyclopedic tumour analysis to treat patients advanced refractory head and neck cancers
Presenter: Rajnish Nagarkar
Session: Poster display session
Resources:
Abstract
372P - Real-world fusion landscape in advanced Chinese pancreatic cancer using next generation sequecing: A multicenter study
Presenter: Yiyu Shen
Session: Poster display session
Resources:
Abstract
373P - Molecular profiling of non-small cell lung cancer (NSCLC) in Asia with targeted next-generation sequencing (NGS): Interim analysis of a co-operative group study (ATORG-001)
Presenter: Aaron Tan
Session: Poster display session
Resources:
Abstract
374P - Circulating tumour DNA (ctDNA) identifies actionable genetic alterations in Middle Eastern and Asian (MEA) patients diagnosed with carcinoma of unknown primary (CUP)
Presenter: Nir Peled
Session: Poster display session
Resources:
Abstract
375P - Whole-exome sequencing of tumour-only samples reveals the association between somatic alterations and clinical features in pancreatic cancer
Presenter: Huixin Lin
Session: Poster display session
Resources:
Abstract
376P - Adoption of molecular testing in breast cancer in a tertiary care center in a developing country
Presenter: Prasanta Dash
Session: Poster display session
Resources:
Abstract
377P - NGS in advanced NSCLC in a developing country: Ready for prime time?
Presenter: Amrith B P
Session: Poster display session
Resources:
Abstract
378P - Germline BRCA1/2 testing: Trend in Tan Tock Seng Hospital Singapore
Presenter: Chia Wei Lim
Session: Poster display session
Resources:
Abstract
379P - Study of germline mutations in high risk cancer patients from a tertiary care center in India
Presenter: Padmaj Kulkarni
Session: Poster display session
Resources:
Abstract
380P - Ventricular–Subventricular zone involvement: A predictive factor for survival in glioblastoma
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract