FDA Approves First Therapy for Lung and Thyroid Cancers with a Certain Genetic Alteration


Selpercatinib is the first therapy approved specifically for cancer patients with rearranged during transfection (RET) gene alterations.

Officials with the FDA have approved selpercatinib, 40 mg & 80 mg capsules (Retevmo, Loxo Oncology), to treat 3 types of tumors—non-small cell lung cancer (NSCLC), medullary thyroid cancer, and other types of thyroid cancers—in patients whose tumors have an alteration in a specific gene. Selpercatinib is the first therapy approved specifically for patients with cancer with rearranged during transfection (RET) gene alterations.1,2

The drug is indicated for metastatic RET fusion-positive NSCLC, advanced medullary thyroid cancer (MTC) or MTC that has spread, in patients aged 12 years and older who require systemic therapy, and advanced RET fusion-positive thyroid cancer in patients aged 12 years and older that requires systemic therapy that has stopped responding to radioactive iodine therapy or is not appropriate for radioactive iodine therapy.1,2

“Innovations in gene-specific therapies continue to advance the practice of medicine at a rapid pace and offer options to patients who previously had few,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, in a prepared statement.1

Selpercatinib is a selective RET kinase inhibitor. According to Lilly, the parent company of Loxo Oncology, selpercatinib may affect both tumor cells and healthy cells, which can result in adverse effects.2

The drug is an oral prescription medicine, 120 mg or 160 mg based on weight, taken twice daily until disease progression or unacceptable toxicity.2

Selpercatinib was approved under the FDA's Accelerated Approval regulations based on the LIBRETTO-001 Phase 1/2 trial's endpoints of objective response rate (ORR) and duration of response (DoR). Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.2

"In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases," said Alexander Drilon, MD, acting chief of early drug development at Memorial Sloan Kettering Cancer Center and lead investigator for LIBRETTO-001, in a prepared statement. "The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy.”2

Selpercatinib was evaluated in the single-arm, multi-center phase 1/2 LIBRETTO-001 trial, the largest trial (N=702) of patients with RET-driven cancers, according to Lilly. The trial enrolled both treatment-naive patients and heavily pretreated patients with a variety of advanced solid tumors including RET fusion-positive NSCLC, RET-mutant MTC, RET fusion-positive thyroid cancer, and certain other solid tumors with RET alterations. Major efficacy outcomes were ORR and DoR, assessed by a blinded independent review committee. Prespecified secondary endpoints included central nervous system (CNS) ORR and CNS DoR.2

Up to 50% of patients with RET fusion-positive NSCLCs can have tumors that metastasize to the brain. Among previously treated NSCLC patients with measurable brain metastases, 10 of 11 patients observed intracranial responses (CNS ORR), with all 10 patients experiencing a CNS DoR of greater than or equal to six months.2

The labeling for Lilly’s selpercatinib product contains warnings and precautions for hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing, and embryo-fetal toxicity. In the LIBRETTO-001 trial, there was a 5% discontinuation rate due to adverse reactions (ARs).2

The most common ARs, including laboratory abnormalities, (≥25%) were increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation. In addition, the most frequent serious AR (≥ 2%) was pneumonia.2


  • FDA Approves First Therapy for Patients with Lung and Thyroid Cancers with a Certain Genetic Mutation or Fusion [news release]. Silver Spring, MD; May 8, 2020: FDA website. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-lung-and-thyroid-cancers-certain-genetic-mutation-or-fusion Accessed May 10, 2020.
  • Lilly Receives U.S. FDA Approval for Retevmo™ (selpercatinib), the First Therapy Specifically for Patients with Advanced RET-Driven Lung and Thyroid Cancers [news release]. Indianapolis, IN; May 8, 2020: Lilly website. https://investor.lilly.com/news-releases/news-release-details/lilly-receives-us-fda-approval-retevmotm-selpercatinib-first Accessed May 10, 2020.

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