Exposure‐Response Relationships for Pralsetinib in Patients with RET‐Altered Thyroid Cancer or RET Fusion‐Positive Nonsmall Cell Lung Cancer

• DOI: 10.1002/jcph.2409
• Publication Date: 2024-02-10T03:33:46Z
• Authors: Nastya Kassir; David McDougall; Denison Kuruvilla; Sean Kim; Shaun Kumar; Ahmadur Rahman; Thorsten Ruf; Sravanthi Cheeti; Wendy Ankrom
• Keywords: Male; Adult; Aged, 80 and over; 0303 health sciences; Lung Neoplasms; Dose-Response Relationship, Drug; Pyridines; Proto-Oncogene Proteins c-ret; Antineoplastic Agents; Pyrimidinones; Middle Aged; Progression-Free Survival; 03 medical and health sciences; Pyrimidines; Carcinoma, Non-Small-Cell Lung; Humans; Pyrazoles; Female; Thyroid Neoplasms; Protein Kinase Inhibitors; Aged

Abstract Pralsetinib is a highly potent oral kinase inhibitor of oncogenic RET (rearranged during transfection) fusions and mutations. received approval from the United States Food Drug Administration for treatment patients with metastatic fusion‐positive non‐small cell lung cancer (NSCLC), accelerated thyroid cancer. Exposure–response (ER) analyses efficacy were performed separately in NSCLC, but data all pooled safety analysis. ER models developed time‐varying exposure; effect covariates was also examined. For higher starting dose associated improved progression‐free survival (PFS), this improvement did not correlate exposure overall. Significant included sex baseline Eastern Cooperative Oncology Group (ECOG) score. cancer, PFS. prior systemic therapy ECOG safety, greater risk grade ≥3 anemia, pneumonia, lymphopenia. Patients an score ≥1 had increased pneumonia. Non‐White lower analysis revealed that pralsetinib PFS NSCLC. However, (ie, 400 vs ≤300 mg daily) correlated better indications. Higher adverse events (AEs); however, overall incidence these acceptably low (≤20%). This supports use pralsetinib, allowing reduction event AEs.