Pralsetinib is approved for the treatment of patients with metastatic, RET fusion–positive non-small cell lung cancer.
RET fusion–positive non–small cell lung cancer (NSCLC) os detected by an FDA-approved test.
Phase 1/2 ARROW trial, in which treatment with pralsetinib elicited durable clinical responses in patients with RET fusion–positive disease who had or had not received previous treatment, irrespective of RET fusion partner or central nervous system involvement.
Results demonstrated an overall response rate (ORR) of 57% and a complete response (CR) rate of 5.7% in a total of 87 patients with NSCLC who received prior treatment with platinum-based chemotherapy.
Moreover, the median duration of response (DOR) has not yet been reached.
Among treatment-naïve patients, the ORR was 70%. with a CR rate of 11%.
Adverse effects include: fatigue, constipation, musculoskeletal pain, and increased blood pressure.
The FDA has also granted pralsetinib a priority review for use in patients with advanced or metastatic RET-mutant medullary thyroid cancer and RET fusion–positive thyroid cancer.
Pralsetinib approved for the treatment of adult patients with metastatic RET fusion–positive non–small cell lung cancer (NSCLC) as detected by an FDA approved test.
Pralsetinib is a once-daily oral RET-targeted therapy designed to inhibit RET alterations.
RET alterations drive a number of cancer types.
RET drives approximately 1% to 2% of patients with NSCLC.
RET is 1 of 7 NSCLC biomarkers that can be targeted with an FDA-approved therapy.
Phase 1/2 ARROW clinical trial demonstrated its efficacy in patients with RET fusion–positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement.
In 87 patients previously treated with platinum-based chemotherapy, the overall response rate was 57% with a 5.7% complete response (CR) rate.
80% of responding patients had responses that lasted 6 months or longer.
The overall response rate was 70% among the 27 treatment-naïve patients who were ineligible for platinum-based chemotherapy per the study protocol, with 11% of patients showing a CR.
Median duration of response was 9.0 months with 58% of patients having responses that lasted 6 months or longer.
The phase 1/2 ARROW trial is an open-label, first-in-human study designed to evaluate the safety, tolerability, and efficacy of pralsetinib administered in patients with RET fusion–positive NSCLC, RET-mutant medullary thyroid cancer (MTC), RET fusion–positive thyroid cancer, and other RET-altered solid tumors.
Pralsetinib approved for the treatment of patients with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory.
Gavreto is the tradename.
Approved pralsetinib for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy or RET fusion-positive thyroid cancer who require systemic therapy and who are refractory to radioactive iodine.
Phase 1/2 ARROW trial evaluated in patients with RET fusion–positive non–small cell lung cancer (NSCLC), RET-mutated MTC, RET fusion–positive thyroid cancer, and other RET-altered solid tumors.
RET fusion–positive alterations are found through the use of next-generation sequencing, fluorescence in situ hybridization, or other tests.
Among 55 patients with advanced or metastatic RET-mutant MTC who had received prior cabozantinib or vandetanib, pralsetinib elicited an ORR of 60%.
79% percent of responders experienced responses that persisted for 6 months or longer.
Among 29 patients with RET-mutant MTC who were treatment naive pralsetinib induced an even higher overall response rate of 66%, and
84% of these patients had responses that persisted for 6 months or longer.
Among patients with RET fusion positive thyroid cancer who were also refractory to radioactive iodine, the ORR reported with pralsetinib was 89%.
All responders experienced responses that lasted for 6 months or longer.
Adverse effects reported in 25% of patients or more included constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea.
Pralsetinib was well tolerated, while demonstrating robust and durable anti-tumor activity when treating heavily pretreated patients with multiple RET fusion–positive advanced solid tumors.arrow
Grade 3/4 laboratory abnormalities that were reported in 2% or. more of participants: decreased lymphocytes, reduced neutrophils, decreased hemoglobin, reduced phosphate, decreased calcium, decreased sodium, increased aspartate aminotransferase, increased alanine aminotransferase, a reduction in platelets, and increased alkaline phosphatase.
Pralsetinib induced an overall response rate of 57% in 87 patients with RET positive NSCLC who had received previous treatment with platinum-based chemotherapy; the complete response rate achieved with the agent was 5.7%.
The recommended dose for the use of the agent in adults and pediatric patients aged 12 years or older is 400 mg to be administered orally.
Common adverse events: fatigue, constipation, musculoskeletal pain, and hypertension.
It has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk of impaired wound healing, and risk of embryo-fetal toxicity.
Oncomine Dx Target Test as a companion diagnostic for pralsetinib.
RET fusions can be identified via next-generation sequencing with tumor tissue or liquid biopsies.
The Oncomine Dx Target Test is a qualitative in vitro diagnostic assay that evaluates 23 genes that are known to be clinically associated with NSCLC.
The Oncomine Dx Target Test is also indicated as a companion diagnostic to identify ROS1 fusion–positive NSCLC, BRAF V600E–positive NSCLC and EGFR L858R– and exon deletion–positive NSCLC.
Moreover, the median duration of response (DOR) has not yet been reached.
Among treatment-naïve patients, the ORR was 70%. with a CR rate of 11%.
Adverse effects include: fatigue, constipation, musculoskeletal pain, and increased blood pressure.
The FDA has also granted pralsetinib a priority review for use in patients with advanced or metastatic RET-mutant medullary thyroid cancer and RET fusion–positive thyroid cancer.