FDA Approves Selpercatinib For Pediatric and Adult Patients With RET-Mutated MTC

The indication is for adult and pediatric patients aged 2 years and older with advanced or metastatic RET-mutated medullary thyroid cancer (MTC) who require systemic therapy.

Image credit: Sebastian Kaulitzki | stock.adobe.com

Updated: September 27, 2024 at 4:47PM

The FDA has approved selpercatinib (Retevmo, Eli Lilly and Company) for adult and pediatric patients aged 2 years and older with advanced or metastatic medullary thyroid cancer (MTC) with an RET mutation—detected by an FDA-approved test—who require systemic therapy. The approval comes after findings from the clinical trial LIBRETTO-531 (NCT04211337), which demonstrated efficacy in this patient population.¹

In 2020, selpercatinib received an accelerated approval for patients who were 12 years of age and older. In May 2024, the FDA granted accelerated approval for this indication to include pediatric patients who are 2 years of age and older. Selpercatinib is taken orally and can block the activity of abnormal RET proteins and fusion proteins that involve parts of RET. The recommended selpercatinib dose for pediatric patients aged 2 to less than 12 is based on the body surface area, and for those 12 and older, recommended dose is based on weight.^1,2

LIBRETTO-531 (NCT04211337) is a randomized, multicenter, open-label phase 3 clinical trial that studied selpercatinib in adults and adolescent patients with advanced or metastatic ARET-mutant MTC. Patients were randomly assigned to receive either 160 mg of selprecatinib administered orally twice per day, or 140 mg of cabozantinib (Cometriq; Exelixis, Inc.) once daily or 300 mg of vandetanib (Caprelsa; Sanofi) administered orally once daily. All patients were stratified based on RET mutation (either M918T or other) and intended treatment if randomly assigned to the control arm.^1,3

About the Trial

Trial Name: A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531)

ClinicalTrials.gov ID: NCT04211337

Sponsor: Loxo Oncology, Inc.

Completion Date (Estimated): February 28, 2026

The main efficacy end point was progression-free survival (PFS), which was measured form baseline to progressive disease or death or up to 35 months, as determined by a blinded independent review committee according to RECIST v1.1. Secondary end points included tolerability and efficacy outcomes, such as treatment failure-free survival (TFFS), overall response rate, duration of response, and overall survival (OS).^1,3,4

According to the findings, median PFS was not reached in the selpercatinib arm compared with 16.8 months (95% CI: 12.2, 25.1) in the control arm (HR 0.280 [95% CI: 0.165, 0.475] p < .0001). The clinical benefit of selpercatinib was supported by a pre-specified analysis of patient-reported comparative side effect impact, with patients receiving selpercatinib reporting less time with severe side effects than those who received either cabozantinib or vandetanib.¹

In an earlier analysis, PFS at 12 months was approximately 86.8% (95% CI, 79.8 to 91.6) for those who received selpercatinib and 65.7% (95% CI, 51.9 to 76.4) for those who received either cabozantinib or vandetanib. Median TFFS was not reached in the selpercatinib group and was about 13.9 months in the control group (HR for disease progression, discontinuation due to treatment-related adverse events, or death: 0.25; 95% CI, 0.15 to 0.42; P< .001). At 12 months, TTFS was 86.2% (95% CI, 79.1 to 91.0) in the selpercatinib group and 62.1% (95% CI, 48.9 to 72.8) in the control group. Additionally, OS was favorable for those who received selpercatinib (69.4% [95% CI, 62.4 to 75.8]; control group: 38.8% [95% CI, 29.1 to 49.2]).⁵

The most common adverse events (AEs) were hypertension, edema, dry mouth, fatigue, and diarrhea. Additionally, the most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes, neutrophils, and calcium, as well as increased alanine aminotransferase, alkaline phosphate, blood creatinine, and aspartate aminotransferase.¹ AEs also led to dose reductions in 38.9% of the patients in the selpercatinib group, compared with 77.3% in the control group. Treatment discontinuation was approximately 4.7% and 26.8%, respectively.⁵

REFERENCES

1. US Food & Drug Administration. FDA approves selpercatinib for RET fusion-positive medullary thyroid cancer. News release. September 27, 2024. Accessed September 27, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-ret-fusion-positive-medullary-thyroid-cancer

2. National Library of Medicine. Selpercatinib for Ret-positive lung, medullary thyroid cancers. Selpercatinib for RET-Positive Lung, Medullary Thyroid Cancers - NCI. Accessed September 27, 2024. https://www.cancer.gov/news-events/cancer-currents-blog/2023/selpercatinib-ret-lung-medullary-thyroid

3. A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531). ClinicalTrials.gov identifier: NCT04211337. Updated June 13, 2024. Accessed September 27, 2024. https://clinicaltrials.gov/study/NCT04211337

4. Wirth LJ, Brose MS, Elisei R, et al. LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer. Future Oncol. 2022;18(28):3143-3150. doi:10.2217/fon-2022-0657

5. Hadoux J, Elisei R, Brose MS, et al. Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. N Engl J Med. 2023;389(20):1851-1861 doi: 10.1056/NEJMoa2309719