David S. Hong, MD, the deputy chair of the Department of Investigational Cancer Therapeutics, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center speaks about the ATA 2021 Abstract – Long-term Efficacy and Safety of Larotrectinib in Pts with Advanced TRK Fusion-positive Thyroid Carcinoma.
Link to Abstract:
https://virtual.oxfordabstracts.com/#/event/public/2083/submission/169
Body of the Abstract:
Goal:
Larotrectinib is a first-in-class, highly selective, CNS-active tropomyosin receptor kinase (TRK) inhibitor that has a 75 percent objective response rate (ORR) in 206 evaluable adult and pediatric patients with non-primary CNS malignancies (Hong et al, ASCO 2021). In an extended cohort with longer follow-up, we report on the effectiveness and safety of larotrectinib in TRK fusion-positive thyroid cancer (TC).
Methodologies:
We combined data from three larotrectinib trials for individuals with locally advanced or metastatic TC with an NTRK gene fusion (NCT02576431, NCT02122913 and NCT02637687). ORR was evaluated by an investigator using RECIST v1.1. The deadline for data submission is July 20, 2020.
Findings:
There were 29 patients in all, with a median age of 60 [range 6–80] years. Papillary thyroid cancer (PTC) was found in 20 (69%) patients, follicular thyroid cancer (FTC) in 2 (7%), and anaplastic thyroid cancer (ATC) in 7 individuals (24 percent ). Patients had 0, 1, or 2 prior systemic therapy (with 1 unknown) in 12 (41%) cases, 7 (24%) cases, and 9 (31%) cases, respectively; 22 (76%) patients received prior radioactive iodine. ORR was 71 percent (95 percent confidence interval [CI] 51-87) among 28 evaluable patients, with 2 (7%) complete responses, 18 (64%) partial responses, 4 (14%) stable disease, 3 (11%) progressing disease, and 1 (4%) not identified. Patients with differentiated TC (DTC) had an ORR of 86 percent (95 percent CI 64-97), while those with ATC had an ORR of 29 percent (95 percent CI 4-71). The median time to respond was 1.9 months (range 1.6-3.7). Duration of response, progression-free survival, and overall survival were calculated by Kaplan-Meier to be 81 percent (95 percent CI 60-100), 69 percent (95 percent CI 49-90), and 76 percent (95 percent CI 58-93) at 24 months, respectively. The 24-month values for DTC were 84 percent (95 percent CI 62-100), 84 percent (95 percent CI 63-100), and 92 percent (95 percent CI 62-100). (95 percent CI 78-100). The 6-month readings for ATC were 50 percent (95 percent CI 0-100), 17 percent (95 percent CI 0-46), and 50 percent (95 percent CI 0-100). (95 percent CI 10-90). Two patients (7%) experienced Grade 3 larotrectinib-related adverse events (AEs), however, none of them stopped taking the drug because of them.
Outcomes:
Larotrectinib showed a high ORR and rapid and persistent disease control in patients with TRK fusion-positive DTC and a favorable safety profile. These findings support the use of NTRK gene fusion testing in individuals with advanced TC who require systemic therapy.