Heather A. Wakelee, MD, FASCO

Panelists discuss how despite significant advances in EGFR-targeted therapy, critical unmet needs persist in EGFR-positive non–small cell lung cancer (NSCLC), including the need for better strategies to combat resistance mechanisms, more effective treatments for brain metastases, improved options for uncommon EGFR mutations, and the development of biomarker-driven approaches to optimize sequencing of available therapies.

Panelists discuss how the MARIPOSA trial demonstrated strong efficacy with amivantamab plus lazertinib that appears comparable to FLAURA2’s results with osimertinib plus chemotherapy, although cross-trial comparisons should be interpreted cautiously given differences in study populations and the need for mature overall survival data from both trials.

Panelists discuss how managing adverse events (AEs) with osimertinib requires proactive monitoring and intervention, with monotherapy generally being well-tolerated aside from common AEs like rash and diarrhea.

Panelists discuss how FLAURA2's impressive progression-free survival (PFS) benefit with osimertinib plus chemotherapy was particularly pronounced in patients with extrathoracic metastases, suggesting this combination approach may be especially valuable for this higher-risk population, though careful consideration of individual patient factors and toxicity management remains important in treatment selection.

Panelists discuss how osimertinib monotherapy demonstrated robust progression-free survival and overall survival benefits in FLAURA, while FLAURA2 showed that adding chemotherapy to osimertinib further improved progression-free survival (PFS) although overall survival (OS) data remains immature, leading to ongoing debate about the optimal first-line approach.

Panelists discuss how EGFR tyrosine kinase inhibitors (TKIs) have revolutionized first-line treatment for EGFR-positive non–small cell lung cancer (NSCLC).

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.

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 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 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 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 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 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 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 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 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 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 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.

Heather Wakelee, MD, FASCO, discusses the significance of early data on the use of taletrectinib in patients with ROS1-positive non–small cell lung cancer from the phase 2 TRUST-II trial.

Heather Wakelee, MD, FASCO, discusses unmet needs in cancer care stemming from the ongoing platinum chemotherapy shortage in the United States, highlighting the need for newer, better drugs to help treat patients.

Heather Wakelee, MD, FASCO, discusses the clinical significance of updated data from several key trials evaluating perioperative immunotherapy in early-stage non–small cell lung cancer.

Comprehensive review on various neoadjuvant strategies under review in the setting of resectable non–small cell lung cancer.

Expert oncologists briefly highlight the role of liquid biopsy in the setting of advanced-stage non–small cell lung cancer.

A focused discussion on the use of molecular profiling in early-stage non–small cell lung cancer to inform decisions on adjuvant and neoadjuvant strategies.

A brief review of real-world data behind molecular profiling in non–small cell lung cancer, followed by a discussion on barriers to testing and uptake.

Expert panelists share insight on molecular testing practices across all subtypes of non–small cell lung cancer to optimally inform treatment decisions.

Heather A. Wakelee, MD, discusses therapy options when patients with lung cancer must receive treatment options immediately rather than wait for molecular testing results.

Heather A. Wakelee, MD, medical oncologist, thoracic specialist, professor of medicine at Stanford University, discusses results from the phase III IMpower150 trial in non–small cell lung cancer.

Heather A. Wakelee, MD, professor of medicine, Stanford University Medical Center, discusses the rationale to explore osimertinib (Tagrisso) in combination with concurrent chemotherapy in patient with EGFR-mutant non–small cell lung cancer.

Heather A. Wakelee, MD, professor of medicine (oncology), Stanford University Medical Center, discusses osimertinib and its role in treating patients with EGFR-mutant non–small cell lung cancer.