Pralsetinib Gains Regular Approval For NSCLC With RET Gene Fusions

The FDA has granted regular approval to pralsetinib as a treatment for adults with metastatic RET fusion-positive non-small cell lung cancer (NSCLC).¹

The FDA has previously granted pralsetinib accelerated approval for this indication in 2020. The accelerated approval was supported by the overall response rate (ORR) and duration of response (DOR) data that were reported in the phase 1/2 ARROW trial (NCT03037385), which included 114 patients with the disease.

The conversion to full approval is backed by data from an additional 123 patients and additional 25 months of follow-up to confirm the durability of response. The new study population included a total of 237 patients with locally advanced or metastatic RET fusion-positive NSCLC. In the treatment-naïve cohort (n = 107), the ORR was 78% (95% CI, 68%-85%), and the median DOR was 13.4 months (95% CI, 9.4-23.1). In the remaining 130 patients who had been pretreated with a platinum-based chemotherapy, the ORR was 63% (95% CI, 54%-71%), and the median DOR was 38.8 months 995% CI, 14.8-not estimable).

Pralsetinib is also approved for patients who are 12 years and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory.² In July 2023, the agent lost its indication for patients with RET-mutated medullary thyroid cancer.

The recommended dose for patients is 400 mg once daily. Patients should take the oral medication on an empty stomach—there should be no food intake for at least 2 hours before and at least 1 hour following the patient taking the medicine. Pralsetinib is available in 100 mg capsules.

Of note, the prescribing label comes with warnings for interstitial lung disease (ILD)/pneumonitis, hypertension, hepatotoxicity, hemorrhage events, tumor lysis syndrome, impaired wound healing, and embryo-fetal toxicity.

If grade 1 or 2 ILD occurs, the treatment should be withheld until resolution and then resumed at a lower dose. For recurrent ILD, the treatment should be permanently discontinued.

Blood pressure should be monitored at least monthly and patients with uncontrolled hypertension should not receive this treatment.

Prior to initiating treatment, patient should have their alanine transaminase (ALT) and aspartate aminotransferase (AST) monitored. During their first 3 months of treatment, they should undergo ALT/AST monitoring every 2 weeks—monitoring should be monthly thereafter. Patients should be closely monitored for tumor lysis syndrome and hemorrhage events. Lastly, patients undergoing elective surgery will need to have their treatment withheld for at least 5 days beforehand. Following surgery, patients should not receive pralsetinib for at least 2 weeks to allow for adequate wound healing.

The most common adverse events associated with treatment are musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough.

Coadministration with strong or moderate CYP3A inhibitors and/or P-gp inhibitors, as well as strong or moderate CYP3A inducers, should be avoided. If coadministration cannot be avoided, the dose of pralsetinib should be modified with CYP3A inducers.

References

1. FDA approves pralsetinib for non-small cell lung cancer with RET gene fusions. FDA. News release. August 9, 2023. Accessed August 9, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pralsetinib-non-small-cell-lung-cancer-ret-gene-fusions
2. Gavreto. Prescribing information. Genentech, Inc; 2023. Accessed August 9, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213721s009lbl.pdf