Is platinib a targeted drug for the treatment of RET mutations?

Pralsetinib is an oral, small-molecule inhibitor of the tyrosine kinase receptor encoded by the proto-oncogene RET (rearranged during transfection), which is mutated or altered in several cancers, including 1% to 2% of non-small cell lung cancer (NSCLC) and approximately 10% of other thyroid cancers. Platinib was found to be a potent inhibitor of cell growth and proliferation in tumor cell lines and experimental tumor models harboring RET mutations or RET gene fusions. In open-label trials of platinib in patients with advanced or metastatic NSCLC with RET alterations, objective response rates ranged from 56% to 85%.

Platinib received accelerated approval for use in the United States in 2020 and was subsequently fully approved. It has shown efficacy in several other solid tumors containing RET gene alterations. Platinib is available in 100 mg capsules under the brand name Gavreto. The recommended dose for adults and children 12 years or older is 400 mg once daily.

Platinib side effects are common and may include dry mouth, diarrhea, constipation, abdominal pain, nausea, systemic arterial hypertension, myalgia, fever, cough, edema, anemia, neutropenia, and increased serum creatinine, uric acid, and transaminases levels. Uncommon but potentially serious adverse events include interstitial pneumonitis, severe hypertension, bleeding events, tumor lysis syndrome, impaired wound healing, and embryo-fetal toxicity. In pre-registration trials, adverse events resulted in dose interruption in 60% of platinib-treated patients, dose reduction in 36% of patients, and permanent discontinuation in 15% of patients. Death from treatment-related adverse events was rare (<1%) and was usually due to sepsis or pneumonia.