Long-term safety of selpercatinib for Rearranged during transfection (RET)-activated advanced solid tumors in LIBRETTO-001: differing patterns of adverse events over time.

Autor:	Raez, Luis E, Massey, Ashish C, Barker, Scott S, Peterson, Patrick M, Liming, Katherine, Pennell, Nathan A
Předmět:	THERAPEUTIC use of antineoplastic agents DIARRHEA POISSON distribution THYROID gland tumors DRUG side effects PATIENT safety RESEARCH funding DATA analysis ANTINEOPLASTIC agents CLINICAL trials HYPERTENSION FATIGUE (Physiology) EDEMA LOGISTIC regression analysis COLORECTAL cancer TREATMENT effectiveness CANCER patients DESCRIPTIVE statistics TREATMENT duration PANCREATIC tumors KAPLAN-Meier estimator STATISTICS ALANINE aminotransferase LUNG cancer CONFIDENCE intervals HYPONATREMIA PHARMACODYNAMICS EVALUATION
Zdroj:	Oncologist; Dec2024, Vol. 29 Issue 12, p1068-1078, 11p
Abstrakt:	Background Selpercatinib is a selective RET inhibitor approved for treatment of RET -activated cancers. Adverse events (AEs) are manageable with dose modifications. This post hoc analysis characterized selpercatinib's clinical safety profile after long-term follow-up in the safety population of LIBRETTO-001. Patients and Methods LIBRETTO-001 is an ongoing phase I/II, single-arm, open-label trial (NCT03157128). Eligible patients were ≥18 years old with diagnosis of advanced/metastatic RET fusion-positive solid tumor, RET -mutant medullary thyroid cancer, or other RET -activated tumors. In phase I, patients received selpercatinib 20 mg QD or 20-240 mg BID; patients in phase II received 160 mg BID. The analyzed population comprised all patients who received ≥1 selpercatinib dose and were followed up until data cutoff (January 13, 2023). Results For the 837 patients, median follow-up was 45.4 months (95% CI, 44.5-46.6); median time on treatment was 30.1 months (range 0.1-66.8). Grade ≥3 treatment-emergent AEs (TEAEs) were reported in 76.2% of patients; most common events were hypertension (19.7%), ALT increased (11.8%), and hyponatremia (9.2%). Serious TEAEs were reported in 51.4% of patients. Most frequently reported any-grade AEs at <6 months of treatment were fatigue (36.6%), dry mouth (32.8%), and ALT increased (30.5%); at ≥24 months of treatment, these were edema (63.2%), diarrhea (60.7%), and fatigue (53.0%). Selpercatinib-related TEAEs leading to reduced dosage were reported in 39.3%, those leading to treatment interruption were reported in 47.1%, and those leading to discontinuation were reported in 4.3% of patients. Conclusion Long-term treatment with selpercatinib is feasible. AEs are manageable with dose modifications, allowing most patients to continue safely on therapy. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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