On September 21, 2022, selpercatinib was granted accelerated approval for adults with locally advanced or metastatic solid tumors with RET gene fusion whose disease has progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.¹ On the same day, selpercatinib was granted regular approval for adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) with RET gene fusion, as detected by a U.S. Food and Drug Administration (FDA)-approved test.¹ The FDA also approved the Oncomine Dx Target Test as a companion diagnostic for selpercatinib.

Supporting Efficacy Data

Accelerated approval and regular approval were based on findings in the multicohort LIBRETTO-001 trial (ClinicalTrials.gov identifier NCT03157128). Among 41 patients with tumors other than NSCLC and thyroid cancer, an objective response was observed in 18 (44%), with a complete response in 2 (5%). The median duration of response was 24.5 months, with 67% of responses lasting at least 6 months. Efficacy was supported by data from patients with RET fusion–positive NSCLC and thyroid cancer in the same trial already described in product labeling.

Conversion to regular approval in NSCLC was based on findings in an additional 172 patients and 18 months of further follow-up. Among a total of 316 patients, an objective response was observed in 84% of 69 treatment-naive patients (complete response in 6%); the median response duration was 20.2 months, with 50% of responses lasting at least 12 months. An objective response was observed in 61% of 247 patients with previous platinum-based chemotherapy (complete response in 7%); the median response duration was 28.6 months, with 63% of responses lasting at least 12 months.

How It Is Used

For both indications, patients should be selected for treatment based on the presence of a RET gene fusion. An FDA-approved companion diagnostic test for the detection of RET fusions in tumors other than NSCLC and thyroid cancer is not currently available.

For both indications, the recommended oral selpercatinib dose based on body weight is 120 mg twice daily for those up to 50 kg and 160 mg twice daily for those 50 kg or more, with treatment continued until disease progression or unacceptable toxicity.

Safety Profile

Safety data come from 796 patients with RET gene fusion or gene mutation–positive advanced solid tumors who received selpercatinib at 160 mg twice daily in LIBRETTO-001. The most common adverse events of any grade were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), constipation (33%), rash (33%), nausea (31%), and headache (28%). The most common grade 3 or 4 adverse events included hypertension (20%), diarrhea (5%), and prolonged QT interval (5%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (20%), increased alanine aminotransferase (12%), and increased aspartate aminotransferase (11%).

Serious adverse events occurred in 44% of patients, most commonly (≥ 2%) pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. Treatment was discontinued because of adverse events in 8%. Fatal adverse events occurred in 3% of patients, including sepsis in six, respiratory failure in five, hemorrhage in four, pneumonia in three, pneumonitis in two, cardiac arrest in two, sudden death in one, and cardiac failure in one.

Selpercatinib has warnings/precautions for hepatotoxicity, interstitial lung disease/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor-lysis syndrome, risk of impaired wound healing, hypothyroidism, and embryofetal toxicity.

REFERENCE

1. Retevmo (selpercatinib) capsules prescribing information, Eli Lilly and Company, September 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213246s007lbl.pdf. Accessed November 16, 2022.