FDA Approves Pralsetinib as a RET Fusion+ NSCLC Treatment


Approval of pralsetinib for the treatment of RET fusion-positive non–small cell lung cancer in based on positive results from the phase 1/2 ARROW trial.

  • Pralsetinib 400 mg is the FDA-recommended dose of the drug for the treatment of metastatic RET fusion-positive non–small cell lung cancer (NSCLC).

  • The approval application for pralsetinib was previously granted breakthrough therapy designation and orphan drug designation nby the FDA.

  • This conversion to regular approval is supported by data from an additional 123 patients and 25 months of additional follow-up to assess durability of response.

The FDA has granted regular approval the RET tyrosine kinase inhibitor, pralsetinib (Gavreto), for the treatment of adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA-approved test.1

Approval of pralsetinib for this indication has been granted based on results from the phase 1/2 ARROW trial (NCT03037385) in which the drug achieved durable responses in patients, while displaying a favorable safety profile.

According to findings assessed by blinded independent review committee, the objective response rate (ORR) observed with pralsetinib in the ARROW study was 78% (95% CI, 68-85). The median duration of response (DOR) observed was 13.4 months (95% CI, 9.4-23.1). Importantly, in the subgroup of patients who were previously treated with platinum-based chemotherapy, the ORR was 63% (95% CI, 54-71), and these patients had a median DOR of 38.8 months (95% CI, 14.8 to not estimable).

Safety findings showed that most common adverse events (AEs) observed with pralsetinib were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough.1 The most common grade 3-4 treatment-related adverse events (TRAEs) in treatment-naive patients with RET fusion-positive NSCLC who received pralsetinib by the data cutoff (n = 116), were neutropenia (18%), hypertension (10%), increased blood creatine phosphokinase (9%), and lymphopenia (9%). A total of 7% (20/281) of patients discontinued treatment due to TRAEs, according to findings previsouly published in the Annals of Oncology.2

Lung cancer in human body | | Image Credit: © blueringmedia -www.stock.adobe.com

lungs | Image Credit: © blueringmedia -www.stock.adobe.com

In the RET fusion-positive NSCLC cohorts of the study, eligible patients must have had a documented RET fusion as determined by local testing of tumor or circulating tumor nucleic acid (ctDNA) in blood. Regardless of their eligibility for standard platinum-based chemotherapy, treatment-naive patients with RET fusion-positive NSCLC were enrolled following a protocol amendment in July of 2019.

The median age for all patients enrolled with RET fusion-positive NSCLC (n = 233) was 60 years (range, 26-87). Less than half of the patients were male (n = 111; 48%), 52% were White, 39% were Asian, and the remaining 9% were other/unknown. Thirty-six percent of patients were current or former smokers compared with 62% who had never smoked. Most patients (64%) had an ECOG performance status of 1, 37% had brain metastases, 70% had KIF5B fusions, 18% had CCDC6 fusions, and about 12% had NCOA4 or other fusions.

The co-primary end points of the study included ORR, complete response, or partial response, in the phase 2 portion of the study. Secondary end points were duration of response, time from first response until disease progression or death, clinical benefit rate, disease control rate, progression-free survival, overall survival, and correlation of RET gene alteration and efficacy.

Based on the study results, the FDA recommends that pralsetinib be administered orally at 400 mg daily without food in the patient’s system for at least 2 hours.


`. FDA approves pralsetinib for non-small cell lung cancer with RET gene fusions. News release. FDA. 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. Griesinger F, Curigliano G, Thomas M, et al. Safety and efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial.. 2022;33(11):1168-1178. doi:10.1016/j.annonc.2022.08.002

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