Selpercatinib: A Review in Advanced RET Fusion-Positive NSCLC

Selpercatinib (Retevmo®/Retsevmo®) is an orally-administered, selective inhibitor of rearranged during transfection (RET) kinase approved for the treatment of advanced RET fusion-positive non-small cell lung cancer (NSCLC). In a pivotal phase 1/2 clinical trial in this population, selpercatinib treatment was associated with robust and durable responses, including intracranial responses, in patients previously treated with platinum-based chemotherapy, as well as in treatment-naïve patients. Selpercatinib had a manageable tolerability profile and an acceptable safety profile; adverse events could generally be managed with dose reductions and only a small proportion of patients discontinued selpercatinib due to treatment-related adverse events. The most common treatment-related adverse events that were grade 3–4 in severity were hypertension, elevated alanine aminotransferase and elevated aspartate aminotransferase. Thus, currently available evidence suggests that selpercatinib is a promising new RET-targeted therapy option for patients with advanced RET fusion-positive NSCLC. Targeted therapy against the oncogenic driver in tumours carrying such mutations offers the potential for greater anti-tumour efficacy and limited off-target toxicity. Fusion of the rearranged during transfection (RET) gene with another gene is one such driver in a small subset of patients with non-small cell lung cancer (NSCLC). Selpercatinib (Retevmo®/Retsevmo®) is a selective RET kinase inhibitor that is taken orally for the treatment of advanced NSCLC with an RET gene fusion. In the pivotal clinical trial in these patients, selpercatinib demonstrated durable responses both in patients previously treated with platinum-based chemotherapy and patients with no prior treatment. Selpercatinib also demonstrated anti-tumour activity against brain metastases associated with NSCLC. Adverse events with selpercatinib were generally manageable with dose reductions and few patients discontinued selpercatinib due to adverse effects. Thus, current data suggest that selpercatinib is a promising new RET-targeted treatment option for advanced RET fusion-positive NSCLC.