News from the FDA/CDC

Pralsetinib: Second drug for RET+ NSCLC approved in U.S.


A second drug is now available in the United States for use in the treatment of patients with metastatic non–small cell lung cancer (NSCLC) that tests positive for rearranged during transfection (RET) fusions.

The new drug is pralsetinib (Gavreto). The Food and Drug Administration granted it an accelerated approval for this indication on the basis of response rate data. Continued approval for this indication depends on clinical benefit in a confirmatory trial.

Pralsetinib joins selpercatinib (Retevmo), which was approved in the United States in May 2020 as the first RET-targeted therapy. Selpercatinib is also indicated for use in RET+ NSCLC and was approved for use in RET+ medullary thyroid cancer and RET+ thyroid cancer.

Pralsetinib is still awaiting approval for these thyroid cancer indications.

Both drugs are taken orally; pralsetinib is taken once daily, and selpercatinib is taken twice daily.

For both drugs, before treatment is initiated, laboratory testing is needed to show that a RET gene alteration is present in the tumor.

RET fusions are found in approximately 1%-2% of patients with NSCLC.

They are the latest of a number of tumor-specific gene alterations found in NSCLC that are targeted with an approved drug.

“Targeted therapies have dramatically improved care for patients with non–small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or Gavreto, marks another milestone in a paradigm shift toward precision medicine,” Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a press release.

Dr. Subbiah was an investigator of the phase 1/2 clinical trial known as ARROW, which provided the data on which the accelerated approval was based. In this trial, patients with RET+ NSCLC were found by testing with next-generation sequencing, FISH (fluorescence in situ hybridization), or other methods.

The ARROW trial involved one cohort of 87 patients who had previously been treated with platinum-based chemotherapy. In these patients, the overall response rate (ORR) was 57%, the complete response (CR) rate was 5.7%, and the median duration of response (DOR) was not estimable, according to the manufacturer, Blueprint Medicines.

The trial also involved 27 treatment-naive patients who were ineligible for platinum-based chemotherapy per the study protocol. In this group, the ORR was 70%, and the CR rate was 11%. The median DOR was 9.0 months.

“Patients treated with [pralsetinib] had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer,” Dr. Subbiah commented.

“We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases. This approval represents an important advance with the potential to change standards of care for patients with RET fusion-positive NSCLC, who have historically had limited treatment options,” Dr. Subbiah added.

Product information for pralsetinib has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk for impaired wound healing, and risk for embryo-fetal toxicity.

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