Retevmo (selpercatinib -LOXO-292), a novel precision cancer medicine targeting tumors containing a mutated protein known as RET was initially approved by the US Food and Drug Administration in May 2020 for the treatment of non-small cell lung cancer (NSCLC) and other cancers with RET mutations identified by genomic testing. In 2024, the FDA approved selpercatinib (Retevmo) for adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer with a RET mutation. Clinical trial results from the LIBRETTO-531 clinical trial have now demonstrated that Retevmo is superior to Cabometyx (cabozantinib) or Caprelsa (vandetanib) in patients with advanced or metastatic RET-mutant medullary thyroid cancer.
RET in Thyroid Cancer
RET fusions occur when a portion of the chromosome containing the RET gene breaks and rejoins with another piece of chromosome, creating a fusion protein capable of fueling cancer growth. RET alterations occur in roughly 10-20% of papillary thyroid cancers (PTC) and over 60% of medullary thyroid cancers (MTC). Up to half of all RET fusion-positive cancers metastasize to the brain.
Retevmo is an oral precision cancer medicine that is designed to target cancers with genomic alterations in the RET kinase, which include fusions and activating point mutations which lead to overactive RET signaling and uncontrolled cell growth. Retevmo was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach.
- Treatment of Thyroid Cancer
- Frequently Asked Questions About Retevmo
- Precision Cancer Medicines and Thyroid Cancer
Effectiveness was evaluated in LIBRETTO-001 a multicenter, open-label, muti-cohort clinical trial in 65 patients with RET fusion-positive thyroid cancer who were radioactive iodine (RAI)-refractory (if RAI was an appropriate treatment option) and were systemic therapy naïve and patients who were previously treated, in separate cohorts.
The overall response rate was 85% in the 41 previously treated patients and 96% in the 24 systemic therapy naïve patients. Median duration of response was 26.7 months in the previously treated patients.
The multi-center, phase 3 LIBRETTO-531 clinical trial enrolled 291 patients with progressive, advanced multikinase inhibitor-naïve, RET-mutant medullary thyroid cancer. Study participants were randomly assigned 2:1 to receive Retevmo or physician’s choice of Cabometyx at 140 mg daily or Caprelsa at 300 mg once daily as initial treatment for advanced disease. Treatment continued until progressive disease, intolerable toxicity, start of a new anticancer therapy, withdrawn consent, death, or study completion. Retevmo treated patients took significantly longer for their cancers to progress when compared to Cabometyx or Caprelsa. Broad-based genomic testing should be performed on all MTC patients who could potentially benefit receive targeted therapies. The full results of the trial will be reported at an upcoming medical meeting or publication.
The most common side effects of Retevmo are low white blood count, dry mouth, diarrhea, hypertension, fatigue, edema, decreased platelets, rash, and constipation.
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References
- Lilly’s Retevmo (selpercatinib) demonstrates superior progression-free survival compared to approved multikinase inhibitors in RET-mutant medullary thyroid cancer. News release. Eli Lilly and Company. August 22, 2023. Accessed August 22, 2023. https://investor.lilly.com/news-releases/news-release-details/lillys-retevmor-selpercatinib-demonstrates-superior-progression
- International Association for the Study of Lung Cancer. Registrational data from the LIBRETTO-1 trial demonstrate compelling and durable activity of selpercatinib (LOXO-292) in RET fusion-positive lung cancer. Published September 9, 2019. Accessed September 9, 2019.
- FDA approves selpercatinib for lung and thyroid cancers with RET gene mutations or fusions
