Pralsetinib Shows Promise in Patients with RET-Altered Thyroid Cancer

According to findings from phase 1/2 of the ARROW trial, pralsetinib shows promise as a potent, well-tolerated treatment for patients with RET-altered thyroid cancer (Lancet Oncol. 2021 Jun;9(8):491-501.)

“Oncogenic alterations in RET represent important therapeutic targets in thyroid cancer. We aimed to assess the safety and antitumour activity of pralsetinib, a highly potent, selective RET inhibitor, in patients with RET-altered thyroid cancers,” explained Dr Vivek Subbiah, The University of Texas MD Anderson Cancer Center, Houston, and colleagues.

ARROW is a multi-cohort, open-label, registrational, phase 1/2 study done in 13 countries across 71 sites in both community and hospital settings. Eligible patients included those 18 years or older with RET-altered locally advanced or metastatic solid tumors with an Eastern Co-operative Oncology Group performance status of 0-2 (later limited to 0-1 in protocol amendment). Patients recieved 400mg of oral pralsetinib once daily until disease progression, intolerance, withdrawal of consent, or investigator decision.

The primary endpoints for phase 2 patients were overall response rate (ORR; response Evaluation Criteria in Solid Tumours version 1.1; masked independent central review) and safety. Safety was assessed for all patients with RET-altered thyroid cancer. Tumor response was assessed in patients who had received prior treatment, were ineligible for standard therapy, or had previously treated RET-fusion thyroid cancer.

Of the 142 patients enrolled, 122 had RET-mutant medullary, and 20 had RET fusion-positive thyroid cancer. Among patients with baseline measurable disease, 71% (15 of 21; 95% CI 48–89) of patients with treatment-naive RET-mutant medullary thyroid cancer had a response, as did 60% (33 of 55; 95% CI 46-73) in patients who had received prior treatment with cabozantinib and vandetanib, or both. Additionally, the ORR in patients with RET fusion-positive was 89% (8 of 9; 95% CI 52–100).

The most common grade 3 or higher adverse events (AE) included hypertension (17%), neutropenia (13%), lymphopenia (12%), and anemia (10%). A total of 21 patients reported serious treatment-related AEs, with the most frequent being pneumonitis. Five patients discontinued treatment, and one died due to treatment-related AEs.

“Pralsetinib is a new, well-tolerated, potent once-daily oral treatment option for patients with RET-altered thyroid cancer,” concluded Dr Subbiah et al.