Therapeutic Advances in the Management of Patients with Advanced RET Fusion-Positive Non-Small Cell Lung Cancer

Opinion statementScreening for activating driver gene alterations at the time of diagnosis is the standard of care for advanced non-small cell lung cancer (NSCLC). ActivatingRET fusions are identified in approximately 1 –2% of NSCLCs and have emerged as a targetable driver alteration. Selpercatinib and pralsetinib are RET-selective tyrosine kinase inhibitors (TKIs) with encouraging efficacy, intracranial activity, and tolerability that we recommend as first-line therapy. As with use of TKIs in other oncogene-addi cted NSCLCs, development of acquired resistance is pervasive and should be specifically delineated through use of repeat tissue biopsy with genetic profiling at the time of disease progression. If an actionable resistance mechanism emerges for which there is a candidate targeted therapy, combination inhibition should be considered. Alternatively, or in the absence of such findings, platinum doublet chemotherapy or particularly platinum-pemetrexed therapy with or without bevacizumab demonstrates a moderate effect.We would not recommend the routine use of nonselective multi-targeted TKIs such as cabozantinib and vandetanib, which have modest activity but limited tolerability due to predictable off-target effects. Single-agent immunotherapy has minimal activity inRET fusion-positive NSCLC. The role of combination chemotherapy and immunotherapy requires further study but may be considered, particularly in the presence of an activatingKRAS alteration. While further deve...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research