| Autor: |
Subbiah V; Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Hu MI; Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Mansfield AS; Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA., Taylor MH; Developmental Cancer Therapeutics Laboratory, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, USA., Schuler M; Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany., Zhu VW; Department of Medicine, University of California Irvine, Orange, California, USA., Hadoux J; Department of Endocrine Oncology, Gustave Roussy, Villejuif, France., Curigliano G; Clinical Division of Early Drug Development, European Institute of Oncology, IRCCS, Milano, Italy.; Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy., Wirth L; Center for Head and Neck Cancers, Massachusetts General Hospital, Boston, Massachusetts, USA., Gainor JF; Center for Head and Neck Cancers, Massachusetts General Hospital, Boston, Massachusetts, USA., Alonso G; Early Drug Development Unit, Vall d'Hebron University Hospital and Institute of Oncology, Barcelona, Spain., Adkins D; Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA., Godbert Y; Nuclear Medicine and Thyroid Oncology Department, Bergonié Institute Cancer Center, Bordeaux, France., Ahn MJ; Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Cassier PA; Department of Medical Oncology, Centre Léon Bérard, Lyon, France., Cho BC; Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Lin CC; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan., Zalutskaya A; Blueprint Medicines Corporation, Cambridge, Massachusetts, USA., Barata T; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Trask P; Genentech, Inc., South San Francisco, California, USA., Scalori A; F. Hoffmann-La Roche Ltd., Welwyn Garden City, United Kingdom., Bordogna W; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Heinzmann S; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Brose MS; Departments of Otorhinolaryngology; Head and Neck Surgery, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA. |
| Abstrakt: |
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. |
