In LIBRETTO-001, Selpercatinib Continues to Perform in RET-Altered Thyroid Cancers
Selpercatinib led to high response and progression-free survival rates among patients who were treatment naive and pretreated with RET-altered thyroid cancers.
Microscopic photorealistic image of thyroid cancer cells - Generated with Google Gemini AI
Treatment with selpercatinib (Retevmo) continued to deliver durable, robust response among both treatment-naive and previously treated patients with RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer, according to long-term safety and efficacy data from the phase 1/2 LIBRETTO-001 study (NCT03157128).1
Among 837 patients enrolled and at a data cutoff of January 2023, the objective response rate (ORR) was 82.5% (range, (75.3%-88.4%) in patients with RET-mutant MTC who were naive to cabozantinib (Cabometyx) and vandetanib (n =143) and 95.8% (range, 78.9%-99.9%) in patients with RET fusion-positive thyroid cancer who were treatment naive (n = 24). The ORR in patients with previously treated RET fusion-positive thyroid cancer (n = 41) was 85.4% (range, 70.8%-94.4%) and 77.6% (range, 70.2%-84.0%) in those with previously treated RET-mutant MTC (n = 152).
For patients with MTC, the median progression-free survival (PFS) was 41.4 months in those who were pretreated and 41.4 months in those naive to cabozantinib and vandetanib. In the RET fusion-positive thyroid cancer arm, the median PFS was not reached in treatment-naive patients and 27.4 months in pretreated patients. The 3-year PFS rate was 75.2% in cabotzantinib/vandetanib-naive MTC and 87.3% in treatment-naive thyroid cancer.
“The current analysis demonstrates continued marked efficacy in a larger population of patients with MTC and [thyroid cancer]. Moreover, selpercatinib demonstrates a favorable ORR, durable responses, and a tolerable safety profile both in patients with MTC and [thyroid cancer], without cumulative or late toxic effects,” authors wrote in the study published in the Journal of Clinical Oncology.
Regarding safety, the safety profile of selpercatinib was consistent with previous reports. The most common grade 3 or higher treatment-emergent adverse events (AEs) were hypertension (MTC, 21.6%; thyroid cancer, 15.2%) and increased alanine aminotransferase (9.0%, 6.1%). The most common serious AEs were pneumonia in patients with MTC (4.6%) and abdominal pain and confusional state (both 4.5%) in patients with thyroid cancer.
The LIBRETTO Studies of Selpercatinib in Thyroid Cancer
In June 2024, the FDA granted traditional approval to selpercatinib for the treatment of adult and pediatric patients 2 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory.2 Accelerated approval was initially granted in 2020, and this approval was supported by the LIBRETTO-001 study.
Additional evidence came from the LIBRETTO-121 (NCT03899792) study and included ORR and duration of response (DOR) data from 10 pediatric and young adult patients with RET fusion-positive thyroid cancer. The ORR was 60% (95% CI, 26%-88%), and 83% of patients had an observed DOR at least 12 months.
Data from LIBRETTO-121 also supported the May 2024 accelerated approval of selpercatinib for the treatment of patients aged 2 and older with RET-altered thyroid cancer or solid tumors, marking the first FDA approval of a targeted therapy for patients under the age of 12 with RET alterations.3
Findings from the phase 3 LIBRETTO-531 study (NCT04211337) were presented at the 2023 European Society for Medical Oncology (ESMO) Congress.4 The median PFS for selpercatinib was not reached at a median follow-up of 12 months (95% CI, not estimable [NE]-NE) vs 16.8 months (95% CI, 12.2-25.1) among patients treated with a kinase inhibitor, translating to a 72% reduction in the risk of disease progression or death (HR, 0.280; 95% CI, 0.165-0.475; P <.0001).
REFERENCES:
1. Wirth LJ, Brose MS, Subbiah V, et al. Durability of responsewithselpercatinib in patients with RET-activated thyroid cancer: Long-term safety and efficacyfrom LIBRETTO-001. JClinOncol.2024 Aug 2:JCO2302503. doi: 10.1200/JCO.23.02503. Epub ahead of print. PMID: 39094065.
2. FDA approves selpercatinib for RET fusion-positive thyroid cancer. News release. FDA. June 12, 2024. Accessed June 12, 2024. https://tinyurl.com/3eaamaxu
3. FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors. News release. FDA. May 29, 2024. Accessed May 29, 2024. https://tinyurl.com/3ykektts
4. Hadoux J, Elisel R, Brose MS, et al. Randomized phase III study of selpercatinib versus cabozantinib or vandetanib in advanced, kinase inhibitor-naïve, RET-mutant medullary thyroid cancer. Ann Oncol. 2023;34(suppl 2):LBA3. doi:10.1016/j.annonc.2023.10.103
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