FDA approves pralsetinib for non-small cell lung cancer with RET gene fusions
Regulatory approval: On Aug 9, 2023, the FDA granted regular approval to pralsetinib (Gavreto) for adult patients with metastatic RET fusion–positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. Pralsetinib previously received accelerated approval for this indication in 2020. The regular approval was supported by additional ARROW trial data and longer follow-up assessing durability of response, with ORR and DOR as key endpoints.
FDA regulatory update (regular approval)
On Aug 9, 2023, the US FDA granted regular approval to pralsetinib (Gavreto; Genentech, Inc.) for adult patients with metastatic RET fusion–positive NSCLC, as detected by an FDA-approved test. Pralsetinib had previously received accelerated approval for this NSCLC indication on Sept 4, 2020.
Evidence base
Approval was supported by data from the ARROW trial (NCT03037385), a multicenter, open-label, multi-cohort study. Conversion from accelerated to regular approval was based on an additional 123 patients and ~25 months of additional follow-up to assess durability of response.
Efficacy was demonstrated in 237 patients with locally advanced or metastatic RET fusion–positive NSCLC treated until progression or unacceptable toxicity. Primary efficacy measures were overall response rate (ORR) and duration of response (DOR) per blinded independent review committee (BIRC).
- Treatment-naïve (n=107): ORR 78% (95% CI, 68–85); median DOR 13.4 months (95% CI, 9.4–23.1)
- Previously treated with platinum chemotherapy (n=130): ORR 63% (95% CI, 54–71); median DOR 38.8 months (95% CI, 14.8–not estimable)
Safety and dosing (label highlights)
Most common adverse reactions (≥25%) included musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough. Recommended dose: 400 mg orally once daily, taken on an empty stomach.