Pralsetinib Will No Longer Be Available for RET-Mutated Medullary Thyroid Cancer


Manufacturers are pulling the pralsetinib indication for patients with medullary thyroid cancer. It is still under investigation as a treatment option for patients with non–small cell lung cancer.

Pralsetinib Will No Longer Be Available for RET-Mutated Medullary Thyroid Cancer

Pralsetinib Will No Longer Be Available for RET-Mutated Medullary Thyroid Cancer

Pralsetinib (Gavreto) will no longer be available as a treatment option for patients with advanced or metastatic RET-positive medullary thyroid cancer (MTC), as the manufacturers involved in its development have chosen to withdraw the indication in the United States.1

According to a news release, the decision was made in collaboration with the FDA, because the phase 3 AcceleRET-MTC trial (NCT04760288) needed to convert the agent’s accelerated approval into a full approval is no longer feasible, they said. They also stated that the decision to withdraw the indication was not because of any new safety or efficacy data.2

“[Blueprint Medicines], in partnership with Genentech, remains committed to supporting appropriate treatment continuity for [patients with] MTC in the United States who are currently treated with [pralsetinib], and to supporting patients and healthcare practitioners [to] navigate the near-term impacts of this update,” Blueprint Medicines wrote in the filing.2

Of note, the agent is still under investigation in other confirmatory trials for other indications for which it received accelerated approval, such as RET fusion-positive non–small cell lung cancer (NSCLC).1

Previously, the agent had received accelerated approval for the treatment of patients with RET-mutated MTC who were 12 years of age or older. The approval had been supported by data from the open-label, multicohort ARROW trial (NCT03037385), in which the agent elicited a 60% (95% CI, 46%-73%) overall response rate (ORR) among 55 patients with medullary thyroid cancer who had received pralsetinib after prior treatment with either cabozantinib (Cabometyx) or vandetanib (Caprelsa). Seventy-nine percent of respondents achieved a response that lasted for at least 6 months.3

The ARROW trial is ongoing and has enrolled a total of 589 participants. To be eligible for enrollment, patients needed a pathologically documented nonresectable advanced solid tumor, an oncogenic RET rearrangement or mutation, and an ECOG performance status of 0 or 1.4

Patients were unable to participate if their cancer had a known primary driver alteration besides RET. If, within the 14 days preceding the first drug of the study drug, patients experienced any of the following, they were not allowed to participate: platelet count less than 75 x 109/L, an absolute neutrophil count less than 1.0 x 109/L, hemoglobin less than 9.0 g/dL, aspartate aminotransferase or alanine aminotransferase beyond the upper limit of normal (ULN; 3 times beyond the upper limit if the patient did not have hepatic metastases, and 5 times beyond the upper limit if the patient had hepatic metastases), a total bilirubin count of 1.5 x ULN, an estimated creatinine clearance less than 40 mL/min, or a total serum phosphorus count greater than 5.5 mg/dL. Patients could not have clinically significant cardiovascular disease, a central nervous system (CNS) metastases or primary CNS tumor, or clinically symptomatic interstitial lung disease.4

At the trial’s most recent analysis, 233 patients with RET fusion–positive NSCLC had received treatment. Among the 86 patients who had received previous treatment with platinum-based chemotherapy, the ORR was 61% (95% CI, 50%-71%). This included 5 complete responses (6%).

Among the 27 treatment-naïve patients, the ORR was 70% (95% CI, 50%-86%). This included 3 complete responses (11%). The most common treatment-related adverse events (AEs) included neutropenia (18%), hypertension (11%), and anemia (10%).5


  1. Genentech withdraws use of Gavreto in US for a type of thyroid cancer, says partner Blueprint. Reuters. June 30, 2023. Accessed July 5, 2023.
  2. United States Securities and Exchange Commission: Form 8-K. Blueprint Medicines Corporation. June 30, 2023. Accessed July 5, 2023.
  3. FDA approves pralsetinib for RET-altered thyroid cancers. FDA. December 1, 2020. Accessed July 5, 2023.
  4. 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). Clinical Updated April 28, 2023. Accessed July 5, 2023.
  5. Gainor JF, Curigliano G, Kim DW, et al. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol. 2021;22(7):959-969. doi:10.1016/S1470-2045(21)00247-3
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