Dr Massarelli on Using Selpercatinib and Pralsetinib in Treating Advanced Non-Small Cell Lung Cancer

Erminia Massarelli, MD, PhD, MS, co-director, Lung Cancer and Thoracic Oncology Program, associate professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses considerations for the use of selpercatinib (Retevmo) or pralsetinib (Gavreto) in treating patients with advanced non–­small cell lung cancer (NSCLC) harboring RET fusions.

Both selpercatinib and pralsetinib have been granted regular approval by the FDA for the treatment of adult patients with locally advanced or metastatic NSCLC harboring a RET gene fusion, as detected by an FDA-approved test. Selpercatinib was approved in September 2022, and pralsetinib received approval in August 2023.

Massarelli notes that selpercatinib has demonstrated superiority over chemotherapy given with or without immunotherapy in the first-line treatment of patients with RET fusion–positive NSCLC. Similarly, she explains that pralsetinib has shown efficacy in treating patients with advanced NSCLC harboring RET fusions, making it another valuable therapeutic option for this patient population.

Both selpercatinib and pralsetinib are utilized in clinical practice for the treatment of patients with advanced RET fusion–positive NSCLC, Masserelli explains. These treatments offer patients a more targeted approach, providing a significant benefit over traditional chemotherapy regimens.

She explains that the safety profile of each agent should be considered when making a treatment decision for a patient with NSCLC harboring a RET fusion. The toxicity profiles of selpercatinib and pralsetinib share similarities, including adverse effects (AEs) such as pneumonitis and hypertension. These AEs are typical of RET tyrosine kinase inhibitors (TKIs) and require careful monitoring and management, Massarelli notes. She adds that selpercatinib has also been associated with ascites, although Massarelli explains that this is uncommon. Massarelli mentions that the incidence and severity of AEs may increase with prolonged use of RET TKIs, necessitating ongoing vigilance.

The efficacy and safety profiles of these RET inhibitors underscore their importance in clinical practice, providing new avenues for managing this challenging patient population, Massarelli concludes.