My Treatment Approach: My Treatment Approach: Navigating Genetic Testing and RET-Targeted Treatments in NSCLC

Panelists discuss how the treatment approach for a 67-year-old man with stage IIIB+ non–small cell lung cancer (NSCLC) awaiting mutation testing involves balancing the urgency of initiating therapy with the importance of molecular testing to guide targeted treatment decisions.

Panelists discuss how molecular testing is crucial in guiding treatment for advanced non–small cell lung cancer (NSCLC), emphasizing the prevalence of mutations like BRAF, KRAS, MET, RET, and EGFR, and their impact on selecting targeted therapies.

Panelists discuss the various tests available for detecting genetic mutations in advanced non–small cell lung cancer (NSCLC), including next-generation sequencing (NGS), reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and Sanger sequencing, and explore whether one method is considered the “gold standard” according to the NCCN guidelines. They also address the appropriate use of circulating tumor DNA (ctDNA) testing, comparing it to tissue testing in this disease state.

Panelists discuss strategies for clinicians without access to in-house molecular testing, focusing on how to ensure appropriate turnaround times when outsourcing tests and share insights on the typical timeline for receiving biomarker testing results at their respective institutions.

Panelists discuss how to balance the need for comprehensive biomarker testing with the urgency to initiate treatment in patients with advanced disease and explore situations where treatment might be started before test results are available.

Panelists discuss the initial approach to the management of RET-positive non–small cell lung cancer (NSCLC), focusing on treatment strategies and the role of targeted therapies such as RET inhibitors in first-line treatment.

Panelists discuss their initial impressions of a patient case with RET fusion–positive non–small cell lung cancer (NSCLC), treatment goals for newly diagnosed patients, and the key patient and disease characteristics considered when selecting a first-line treatment regimen.

Panelists discuss the specific factors that influence the decision to initiate one of the NCCN guideline–preferred RET inhibitors, selpercatinib or pralsetinib, over the other in the treatment of RET fusion–positive NSCLC.

Panelists discuss the situations in which other first-line therapies, such as cabozantinib or PD-L1–positive chemotherapy options, might be considered for RET fusion–positive non–small cell lung cancer (NSCLC), and compare the role of chemotherapy and immunotherapy to that of RET inhibitors in this setting.

Panelists discuss the common adverse effects for patients receiving selpercatinib or pralsetinib, strategies for managing these effects, and whether differences in the safety profiles of these drugs influence treatment choices for RET fusion–positive non–small cell lung cancer.

Panelists discuss how to monitor patients for response to treatment and early signs of resistance in RET fusion–positive non–small cell lung cancer (NSCLC), including the approach to follow-up molecular testing, and describe strategies for treatment sequencing after disease progression on RET inhibitors.

Panelists discuss the unmet needs and future perspectives in the treatment of RET-positive non–small cell lung cancer (NSCLC), focusing on areas for improvement in therapy and the potential for new treatment strategies.