WASHINGTON — The FDA approved selpercatinib (Retevmo), a kinase inhibitor, for the treatment of lung and thyroid tumors — non-small cell lung cancer (NSCLC) that has spread in adults, advanced medullary thyroid cancer (MTC) that has spread in patients 12 and older who need systemic therapy, and advanced rearranged during transfection (RET) thyroid cancer in those 12 and older who require systemic therapy and no longer respond to radioactive iodine therapy or for whom that therapy is not appropriate.
In order for patients to be eligible for treatment with selpercatinib, they must undergo laboratory testing to see if they have a RET gene alteration.
This approval was based on the results of clinical trials assessing patients with each of these types of tumors. In the trials, the patients received 160 mg of oral selpercatinib twice daily until disease progression or unacceptable toxicity. “The major efficacy outcome measures were overall response rate (ORR), which reflects the percentage of patients that had a certain amount of tumor shrinkage, and duration of response (DOR),” the FDA noted in its statement.
- In NSCLC, 105 adults with the RET gene alteration who had been previously treated with platinum chemotherapy achieved an ORR of 64%. For most of these patients (81%), their response to treatment lasted at least 6 months. “Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had never undergone treatment,” the agency wrote. “The ORR for these patients was 84%. For 58% of patients who had a response to the treatment, their response lasted at least six months.”
- For MTC, 143 adult and pediatric patients 12 or older “with advanced or metastatic RET-mutant MTC who had been previously treated with cabozantinib, vandetanib or both (types of chemotherapy), and patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib” were enrolled, the FDA explained. Fifty-five patients who were previously treated achieved an ORR of 69%. The response lasted for at least 6 months in 76% of patients who responded to the drug. “Efficacy was also evaluated in 88 patients who had not been previously treated with an approved therapy for MTC,” the FDA wrote. “The ORR for these patients was 73%. For 61% of patients who had a response to the treatment, their response lasted at least six months.”
- For 19 patients 12 and older enrolled with RET fusion-positive thyroid cancer, the outcomes were similar. “The ORR for the 19 previously treated patients was 79%,” the FDA wrote. “For 87% of patients who had a response to the treatment, their response lasted at least six months.” Of note, 8 patients who had not received therapy other than radioactive iodine had an ORR of 100%, and for 75% of those who responded to treatment, that response lasted at least 6 months.
“Retevmo can cause serious side effects including hepatotoxicity (liver damage or injury), elevated blood pressure, QT prolongation (the heart muscle takes longer than normal to recharge between beats), bleeding and allergic reactions,” the FDA warned. “If a patient experiences hepatotoxicity, Retevmo should be withheld, dose reduced or permanently discontinued. Patients undergoing surgery should tell their doctor as drugs similar to Retevmo have caused problems with wound healing.”
Since the drug may harm a developing fetus or newborn, women should be advised of the risks during pregnancy and also that they should not breastfeed while taking the drug.
Other common side effects seen with selpercatinib were increased aspartate aminotransferase and alanine aminotransferase enzymes in the liver, increased blood sugar, decreased white blood cell count, decreased blood calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, swelling, low blood platelet count, increased cholesterol, rash, constipation, and decreased blood sodium.
Selpercatinib received accelerated approval, as well as priority review, breakthrough therapy and orphan drug designations.
Selpercatinib is made by Loxo Oncology, Inc, a subsidiary of Eli Lilly and Company.
Candace Hoffmann, Managing Editor, BreakingMED™
Cat ID: 24
Topic ID: 78,24,110,24,935,65
