RET-mutated non-small cell lung cancer treated with pralsetinib: a case series

Background: Targeted therapies significantly changed the treatment scenario of non-small cell lung cancer (NSCLC) and improved prognosis of patients harbouring oncogenic drivers. Among these, REarranged during Transfection (RET) fusions are rare, occurring in 1% to 2% of NSCLC. Recent trials revealed the efficacy of novel inhibitors such as pralsetinib and selpercatinib. Due to rarity of RET fusion and novelty of these target therapies, observational and “real world” evidence are missing. The purpose of this series is to point out the impact of treatment with pralsetinib in the clinical setting. Case Description: We report the clinical cases of four patients with metastatic RET-positive NSCLC, who achieved clinical benefit and objective response upon treatment with pralsetinib (400 mg/die). All patients received target therapy after failure of chemotherapy or immunotherapy. Three patients experienced adverse events leading to dose reduction (200 mg/die), but none permanently discontinued treatment. Conclusions: To our knowledge this is the first clinical series about pralsetinib treatment for metastatic RET positive NSCLC in a “real world” setting. It proves the importance of investigating and targeting RET fusions in NSCLC patients. According to the literature, patients receiving RET inhibitor appear to have significant and lasting responses.