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Long-term safety of selpercatinib for Rearranged during transfection (RET)-activated advanced solid tumors in
Luis E Raez1, Ashish C Massey2, Scott S Barker2
1Thoracic Oncology Program, Memorial Cancer Institute, Florida Atlantic University (FAU), Pembroke Pines, FL 33026, United States.
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.
Insights
Long-term selpercatinib treatment is feasible for RET-activated cancers. Adverse events are manageable with dose adjustments, enabling continued safe therapy for most patients.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Selpercatinib is an approved selective RET inhibitor for RET-activated cancers.
- Adverse events (AEs) associated with selpercatinib are generally manageable through dose modifications.
- This study presents a long-term safety profile analysis of selpercatinib from the LIBRETTO-001 trial.
Purpose of the Study:
- To characterize the long-term clinical safety profile of selpercatinib.
- To evaluate the feasibility and safety of extended selpercatinib treatment in patients with RET-altered cancers.
- To assess the impact of dose modifications on managing adverse events during long-term therapy.
Main Methods:
- Post hoc analysis of the safety population from the ongoing LIBRETTO-001 (NCT03157128) phase I/II trial.
- Included 837 patients with advanced/metastatic RET fusion-positive solid tumors, RET-mutant medullary thyroid cancer, or other RET-activated tumors.
- Patients received varying doses of selpercatinib, with follow-up until January 13, 2023, for a median of 45.4 months.
Main Results:
- Median follow-up was 45.4 months, with a median treatment duration of 30.1 months.
- Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 76.2% of patients; common events included hypertension and elevated ALT.
- Long-term AEs (≥24 months) included edema, diarrhea, and fatigue, with 4.3% of patients discontinuing due to TEAEs.
Conclusions:
- Long-term administration of selpercatinib is clinically feasible.
- Adverse events associated with selpercatinib can be effectively managed with dose modifications.
- Dose adjustments allow the majority of patients to continue selpercatinib therapy safely over extended periods.
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