https://scholars.lib.ntu.edu.tw/handle/123456789/640202
標題: | Pralsetinib in Patients with Advanced/Metastatic Rearranged During Transfection (RET)-Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study | 作者: | Subbiah, Vivek Hu, Mimi I Mansfield, Aaron S Taylor, Matthew H Schuler, Martin Zhu, Viola W Hadoux, Julien Curigliano, Giuseppe Wirth, Lori Gainor, Justin F Alonso, Guzman Adkins, Douglas Godbert, Yann Ahn, Myung-Ju Cassier, Philippe A Cho, Byoung Chul CHIA-CHI LIN Zalutskaya, Alena Barata, Teresa Trask, Peter Scalori, Astrid Bordogna, Walter Heinzmann, Sebastian Brose, Marcia S |
關鍵字: | RET alteration; RET tyrosine kinase inhibitor; medullary thyroid cancer; patient-reported outcomes; thyroid cancer | 公開日期: | 一月-2024 | 卷: | 34 | 期: | 1 | 來源出版物: | Thyroid : official journal of the American Thyroid Association | 摘要: | Background: Rearranged during transfection (RET) alterations are targetable oncogenic drivers in thyroid cancer. Primary data from the open-label, phase 1/2 ARROW study demonstrated clinical activity and manageable safety with pralsetinib, a selective RET inhibitor, in patients with advanced/metastatic RET-altered thyroid cancer. We present an updated analysis with more patients and longer follow-up. Methods: Adult patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC) or RET fusion-positive thyroid cancer who initiated oral pralsetinib at 400 mg once daily were included. Primary endpoints were overall response rate (ORR) by blinded independent central review (per RECIST v1.1) and safety. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), and overall survival. Responses were assessed in three cohorts of patients with baseline measurable disease: patients with RET-mutant MTC who had received prior cabozantinib and/or vandetanib (C/V), treatment-naïve patients with RET-mutant MTC, and patients with previously treated RET fusion-positive thyroid cancer. Patient-reported outcomes (PROs) were an exploratory endpoint. Results: As of October 18, 2021, the measurable disease population comprised of 61 patients with RET-mutant MTC and prior C/V, 62 treatment-naïve patients with RET-mutant MTC, and 22 patients with RET fusion-positive thyroid cancer who had received prior systemic therapy, including radioactive iodine. The ORR was 55.7% [confidence interval; 95% CI: 42.4-68.5] in patients with RET-mutant MTC and prior C/V, 77.4% [95% CI: 65.0-87.1] in treatment-naïve patients with RET-mutant MTC, and 90.9% [95% CI: 70.8-98.9] in patients with previously treated RET fusion-positive thyroid cancer. Median DoR and median PFS were both 25.8 months in patients with RET-mutant MTC and prior C/V, not reached in treatment-naïve patients with RET-mutant MTC, and 23.6 and 25.4 months, respectively, in patients with previously treated RET fusion-positive thyroid cancer. In the RET-altered thyroid cancer safety population (N = 175), 97.1% of patients reported a treatment-related adverse event (TRAE); these led to discontinuation in 5.7% and dose reduction in 52.6% of patients. There was one death (0.6%) due to a TRAE. PROs improved or remained stable after pralsetinib treatment. Conclusions: In this updated analysis of the ARROW study, pralsetinib continued to show deep and durable clinical activity and a manageable safety profile in patients with advanced/metastatic RET-altered thyroid cancer. Clinical Trial Registration: NCT03037385. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/640202 | ISSN: | 10507256 | DOI: | 10.1089/thy.2023.0363 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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