The U.S. Food and Drug Administration ( FDA ) has approved Gavreto ( Pralsetinib ) for the treatment of adult and paediatric patients 12 years of age and older with advanced or metastatic rearranged during transfection ( RET )-mutant medullary thyroid cancer ( MTC ) who require systemic therapy, or with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory ( if radioactive iodine is appropriate ).
These indications were approved under the FDA’s accelerated approval programme based on data from the phase I/II ARROW study. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
Approximately 10-20% of people with papillary thyroid cancer have RET fusion-positive tumours, and roughly 90% of people with advanced medullary thyroid cancer carry RET mutations.
Biomarker testing for RET fusions and mutations can help identify people who are eligible for treatment with Gavreto.
The approvals are based on results from the phase I/II ARROW study, which has demonstrated durable clinical activity in people with or without prior therapy and regardless of RET alteration genotypes.
Treatment with Gavreto led to an overall response rate ( ORR ) of 60% ( 95% CI: 46%, 73% ) in 55 people with RET-mutant metastatic medullary thyroid cancer previously treated with Cabozantinib and/or Vandetanib, and the median duration of response ( DoR ) was not reached ( 95% CI: 15.1 months, not-estimable ).
In 29 people with Cabozantinib- and Vandetanib-naïve RET-mutant advanced medullary thyroid cancer who were determined to be not eligible for standard therapies, the ORR was 66% ( 95% CI: 46%, 82% ), and the median DoR was not reached ( 95% CI: not-estimable, not-estimable ).
In nine people with RET fusion-positive metastatic thyroid cancer, Gavreto has demonstrated an ORR of 89% ( 95% CI: 52%, 100% ), and the median DoR was not reached ( 95% CI: not-estimable, not-estimable ).
In ARROW trial patients across RET-altered tumour types, the most common adverse reactions ( greater than or equal to 25% ) were constipation, hypertension, fatigue, musculoskeletal pain and diarrhoea.
ARROW trial consists of two parts: a dose escalation portion, which is complete, and an expansion portion in people treated with 400 mg of Gavreto, once-daily.
RET gene alterations, such as fusions and mutations, are key disease drivers in many types of cancer, including non-small-cell lung cancer ( NSCLC ) and several types of thyroid cancers.
Approximately 10-20% of people with papillary thyroid cancer ( the most common type of thyroid cancer ) have RET fusion-positive tumours, and roughly 90% of people with advanced MTC carry RET mutations.
In NSCLC, RET fusions represent approximately 1-2% of patients.
Oncogenic RET fusions also are observed at low frequencies in cholangiocarcinoma, colorectal, neuroendocrine, ovarian, pancreatic and thymus cancers. ( Xagena )
Source: Roche, 2020