Marcia S. Brose, MD, Ph.D. of the Pearlman School of Medicine at The University of Pennsylvania speaks on the ESMO 2020 abstract Larotrectinib treatment of advanced TRK fusion thyroid cancer.
Larotrectinib is an EMA and FDA approved first-in-class, central nervous system active, highly selective tropomyosin receptor kinase (TRK) inhibitor for the treatment of adult and pediatric TRK fusion cancer patients (pts). In pts with TRK fusion cancer across different tumor types (Hong et al. Lancet Oncol. 2020), Larotrectinib provided an objective response rate (ORR) of 79 percent and a median period of response (DoR) of 35.2 months. We report the efficacy and protection of larotrectinib in the TRK fusion thyroid cancer subset of pts here.
Data from two larotrectinib clinical trials (NCT02122913 and NCT02576431) were pooled in pts of locally advanced or metastatic thyroid cancer containing neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Adult and pediatric patients received 100 mg and 100 mg / m2 of larotrectinib twice daily, respectively, on a 28-day, continuous schedule. Investigator-assessed responses were per RECIST v1.1 (data cut-off: 15 July 2019).
With TRK fusion thyroid cancer, a total of 28 pts were included: 19 papillary, 7 anaplastic, and 2 follicular. The median age (range of 6-80) was 62 years. Twelve (43%) pts had a fusion of NTRK1 and 16 (57%) pts had a fusion of NTRK3. Prior treatment, including surgery (100 percent), radiotherapy (61 percent), radioiodine (75 percent), and about 1 prior systemic therapy (89 percent) were obtained by all pts. 3 previous systemic therapies were received by eleven (44 percent) pts. ORR was 75% (95 % confidence interval [CI] 55–89), including 29% for anaplastic disease pts (Table). The DoR range was between 1.9 + and 41.0 + months. Median progression-free survival (PFS) was not attained (95 percent CI 16.6-NE) and 81 percent was the 12-month PFS average. There were mainly Grade 1-2 adverse events (AEs). Grade 3 AEs occurred in 46 percent of pts and grade 3 AEs linked to larotrectinib occurred in 7 percent of pts.
Larotrectinib was highly successful and a favourable safety profile was demonstrated. These results help regular monitoring of non-medullary, advanced thyroid cancer for NTRK gene fusions in pts.