Pralsetinib Approved for Non–Small Cell Lung Cancer With RET Gene Fusions

Lung cancer in chest x-ray.

The FDA has granted regular approval to pralsetinib (Gavreto®, Genentech, Inc.) for adult patients with metastatic rearranged during transfection (RET) fusion–positive non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

Previously, pralsetinib was granted accelerated approval for the NSCLC indication on September 4, 2020, based on the initial overall response rate and duration of response findings in 114 patients. Based on data of the addition of 123 patients and 25 months of follow-up to further assess duration of response, the conversion to regular approval was granted. 

Why it matters: “RET fusions are present in 1% to 2% of NSCLC,” wrote Frank Griesinger, MD, PhD, Head of Clinical Oncology at Pius-Hospital in Oldenburg, Germany, and colleagues, in their updated results of the ARROW trial (NCT03037385). “Pralsetinib, a highly potent, oral, central nervous system–penetrant, selective RET inhibitor, previously demonstrated clinical activity in patients with RET fusion–positive NSCLC.”

What they studied: Safety and efficacy were studied in the phase 1/2 open-label, first-in-human, multicenter trial in which 237 adult patients with locally advanced or metastatic RET fusion–positive NSCLC received 400 mg pralsetinib orally, once daily, until disease progression or unacceptable toxicity.

The primary end points measured were overall response rate and duration of response determined by a Blinded Independent Review Committee.

What they found: Among the treatment-naive population (n=107), the overall response rate was 78% and duration of response was seen at a median of 13.4 months. Among patients previously treated with platinum-based chemotherapy (n=130), the overall response rate was 63% and duration of response was seen at a median of 38.8 months.

Adverse events: The most common adverse events experienced by ≥25% of patients were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough.

What’s next: The ongoing phase 3 AcceleRET Lung trial (NCT04222972) is further studying the efficacy of pralsetinib to provide continued support of the drug for RET fusion–positive NSCLC in the first-line setting.

Conclusion: “We show that orally administered once daily pralsetinib produces a robust overall response rate, including intracranial activity and durable progression-free survival, in patients with advanced RET fusion–positive NSCLC who are treatment-naive or refractory to standard-of-care chemotherapy,” concluded Dr. Griesinger and colleagues.

Instructions: The recommended dosage of pralsetinib is 400 mg orally, once daily, taken on an empty stomach; food should not be eaten 2 hours before and at least 1 hour after.

For More Information

Griesinger F, Curigliano G, Thomas M, et al (2022). Safety and efficacy of pralsetinib in RET fusion–positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial. Ann Oncol, 33(11):1168-1178. DOI:10.1016/j.annonc.2022.08.002 (2023). Phase 1/2 study of the highly-selective RET inhibitor, pralsetinib (BLU-667), in participants with thyroid cancer, non-small cell lung cancer, and other advanced solid tumors (ARROW). NLM identifier: NCT03037385. (2023). A study of pralsetinib versus standard of care for first-line treatment of advanced non-small cell lung cancer (NSCLC) (AcceleRET-Lung). NLM identifier: NCT04222972.

Gavreto® (pralsetinib) prescribing information (2023). Genentech Inc. Available at:

US Food and Drug Administration (2023). FDA approves pralsetinib for non-small cell lung cancer with RET gene fusions. Available at:

Image credit: James Heilman, MD. Licensed under CC BY-SA 4.0

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