Reference Detail

Ref Type

PMID

Authors

M.E. Cabanillas, A. Drilon, A.F. Farago, M.S. Brose, R. McDermott, D. Sohal, D. Oh, M. Almubarak, J. Bauman, E. Chu, S. Kummar, S. Leyvraz, K. Park, J.A. Reeves, L. Dima, P. Maeda, L. Rodrigues, N. Brega, D.S. Hong, S.G. Waguespack

Title

Larotrectinib treatment of advanced TRK fusion thyroid cancer

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	31	suppl_4

URL

https://www.sciencedirect.com/science/article/pii/S0923753420414000

Abstract Text

Background: Larotrectinib is a first-in-class, central nervous system-active, highly selective tropomyosin receptor kinase (TRK) inhibitor approved by the EMA and FDA for the treatment of adult and paediatric patients (pts) with TRK fusion cancer. Larotrectinib produced an objective response rate (ORR) of 79% and a median duration of response (DoR) of 35.2 months in pts with TRK fusion cancer across various tumour types (Hong et al. Lancet Oncol. 2020). Here, we report the efficacy and safety of larotrectinib in the subset of pts with TRK fusion thyroid cancer. Methods: Data in pts with locally advanced or metastatic thyroid cancer harbouring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion were pooled from two larotrectinib clinical trials (NCT02122913 and NCT02576431). Adult and paediatric patients received larotrectinib 100 mg and 100 mg/m2 twice daily, respectively, on a continuous 28-day schedule. Responses were investigator-assessed per RECIST v1.1 (data cut-off: 15 July 2019). Results: A total of 28 pts with TRK fusion thyroid cancer were included: 19 papillary, 7 anaplastic and 2 follicular. Median age was 62 years (range 6–80). Twelve (43%) pts had a NTRK1 fusion and 16 (57%) pts had a NTRK3 fusion. All pts had received prior treatment, including surgery (100%), radiotherapy (61%), radioiodine (75%) and ≥1 prior systemic therapy (89%). Eleven (44%) pts had received ≥3 prior systemic therapies. ORR was 75% (95% confidence interval [CI] 55–89), including 29% for pts with anaplastic disease (Table). DoR ranged from 1.9+ to 41.0+ months. Median progression-free survival (PFS) was not reached (95% CI 16.6–NE) and the 12-month PFS rate was 81%. Adverse events (AEs) were mostly Grade 1–2. Grade ≥3 AEs occurred in 46% of pts and 7% of pts had Grade ≥3 AEs related to larotrectinib. Conclusions: Larotrectinib was highly efficacious and demonstrated a favourable safety profile. These findings support routine testing for NTRK gene fusions in pts with non-medullary, advanced thyroid cancer. Clinical trial identification: NCT02122913, April 25, 2014; NCT02576431, October 15, 2015.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References