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
87P - Negative to positive lymph node ratio-prognostic marker of survival in node positive rectal cancer
Presenter: Pavan Jonnada
Session: Poster display session
Resources:
Abstract
88P - The Sidra LUMC advanced colon cancer NGS cohort
Presenter: Wouter Hendrickx
Session: Poster display session
Resources:
Abstract
89P - A phase II trial of adjuvant chemoradiotherapy for patients with high-risk rectal submucosal invasive cancer after local resection
Presenter: Masaaki Noguchi
Session: Poster display session
Resources:
Abstract
90P - High MICB expression confers prognostic benefit in colorectal cancer
Presenter: Shanchao Yu
Session: Poster display session
Resources:
Abstract
91P - Adjuvant therapy for high-risk stage II or stage III colon adenocarcinoma: A propensity score-matched, nationwide, population-based cohort study
Presenter: Chien-Hsin Chen
Session: Poster display session
Resources:
Abstract
92P - Prospective randomized controlled study comparing primary surgery versus neoadjuvant chemotherapy followed by surgery in gastric carcinoma
Presenter: Vipin Goel
Session: Poster display session
Resources:
Abstract
93P - Biomarker selection of liver metastatic colorectal patients for anti-EGFR monoclonal antibodies: A machine learning analysis
Presenter: Yijiao Chen
Session: Poster display session
Resources:
Abstract
94P - NORTH/HGCSG1003: North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer: Final analysis
Presenter: Michio Nakamura
Session: Poster display session
Resources:
Abstract
95P - Anatomical resections improve relapse-free survival in patients with KRAS/NRAS/BRAF- mutated colorectal liver metastases
Presenter: Ye Wei
Session: Poster display session
Resources:
Abstract
96P - Incidence, characteristics and prognosis in colorectal cancer with CNS metastases
Presenter: Nicola Taylor
Session: Poster display session
Resources:
Abstract