FDA Grants Traditional Approval to Selpercatinib for RET-Fusion Solid Tumors

The Food and Drug Administration (FDA) has converted the accelerated approval of selpercatinib (Retevmo) to a traditional approval for adult and pediatric patients aged 2 years and older with locally advanced or metastatic solid tumors harboring a RET gene fusion.

This indication specifically applies to patients whose disease has progressed on or following prior systemic treatment or those who have no satisfactory alternative treatment options.

Selpercatinib first received accelerated approval for this tissue-agnostic indication in adult patients in 2022, followed by a pediatric expansion in 2024. The transition to traditional approval confirms the clinical benefit of the agent across a broad spectrum of RET-driven malignancies.

Clinical evidence supporting traditional approval

The FDA’s decision was primarily supported by findings from the LIBRETTO-001 trial (NCT03157128), a multicenter, open-label, multi-cohort study. While efficacy was bolstered by data in RET fusion-positive non-small cell lung cancer (NSCLC) and thyroid cancer, the specific evaluation for this approval focused on 75 patients with various other RET fusion-positive solid tumors. All included patients had experienced disease progression on prior systemic therapies or lacked standard alternative options.

The primary efficacy measures for the study were overall response rate (ORR) and duration of response (DOR). Results demonstrated a robust clinical benefit:

• Overall Response Rate: 47% (95% CI: 35, 59).
• Median Duration of Response: 24.5 months (95% CI: 11.2, 49.1).

The breadth of the "tissue-agnostic" label is evidenced by the diverse tumor types that responded to treatment. These included colorectal cancer, pancreatic adenocarcinoma, salivary cancer, soft tissue sarcoma, cholangiocarcinoma, breast cancer, and neuroendocrine tumors, among others.

Pediatric efficacy and safety

For oncology nurses in the pediatric setting, the approval includes data from the LIBRETTO-121 trial (NCT03899792). This trial evaluated selpercatinib in pediatric and young adult patients with locally advanced refractory RET fusion-positive solid tumors. Responses were specifically observed in patients with congenital infantile fibrosarcoma, spindle cell sarcoma, and RET fusion-positive thyroid cancer.

Nursing considerations for safety and monitoring

Oncology nurses play a critical role in the management of patients receiving selpercatinib. The prescribing information includes several warnings and precautions that necessitate diligent monitoring and patient education:

• Hepatotoxicity: Nurses should monitor liver function tests regularly.
• Cardiovascular risks: Monitoring for hypertension and QT interval prolongation is essential.
• Respiratory management: Patients should be assessed for signs of interstitial lung disease (ILD) or pneumonitis.
• Wound healing: Due to the risk of impaired wound healing, selpercatinib should be withheld around the time of elective surgeries.
• Pediatric-specific concerns: In children, nurses must be alert for slipped capital femoral epiphysis (also known as slipped upper femoral epiphysis).
• Other Risks: The label also warns of hemorrhagic events, hypersensitivity, tumor lysis syndrome, hypothyroidism, and embryo-fetal toxicity.

Dosing and administration guidelines

Selpercatinib is administered orally, with dosages determined by body weight for patients aged 12 years and older.

The weight-based guidelines are:

• Body weight < 50 kg: 120 mg twice daily.
• Body weight ≥ 50 kg: 160 mg twice daily.

For pediatric patients between the ages of 2 and 12, healthcare providers should consult the specific prescribing information for specialized dosing instructions. It is critical that biomarker testing with an FDA-approved test is conducted prior to initiation to confirm the presence of a RET gene fusion.

The path forward in precision oncology

The FDA review utilized the Assessment Aid, a voluntary submission from the manufacturer that facilitated a streamlined evaluation, resulting in an approval two months ahead of the goal date. This expedited timeline underscores the priority placed on expanding access to targeted therapies for patients with rare genomic alterations.

Healthcare professionals are encouraged to report any serious adverse events through the FDA's MedWatch Reporting System to continue building the long-term safety profile of this agent. As the oncology community moves toward more personalized care, the traditional approval of selpercatinib reinforces the importance of comprehensive genomic profiling in the initial and subsequent lines of cancer treatment.

Reference

1. Food and Drug Administration. FDA grants traditional approval to selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. Published July 14, 2026. Accessed July 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-selpercatinib-locally-advanced-or-metastatic-ret-fusion-positive