ESMO 2024: Treatment Breakthroughs in Pretreated Patients with Advanced or Metastatic NSCLC With or Without Actionable Genomic Alterations

This episode explores expert insights on the clinical use of osimertinib in the frontline setting for EGFR-mutated NSCLC, the impact of combining osimertinib with platinum-based chemotherapy on progression-free survival (PFS), and the significance of extending PFS by nearly 9 months in patients with advanced NSCLC who are not candidates for curative treatment.

This episode delves into expert perspectives on the safety and tolerability of combining osimertinib with chemotherapy in untreated, advanced EGFR-mutated NSCLC, resistance to third-generation EGFR TKIs, the superiority of concurrent versus sequential therapy from the FLAURA2 study, the role of ctDNA in managing additional EGFR mutations, and decision-making in utilizing FLAURA2 for treatment selection.

This episode reviews the key takeaways from the ADAURA trial, discusses strategies for protecting the CNS in EGFR-mutated NSCLC, and examines the impact ADAURA had on recurrence rates in patients with completely resected EGFR-mutated NSCLC who were previously treated with adjuvant chemotherapy.

Although the NCCN guidelines recommend osimertinib as an adjuvant therapy option, what is your position on its use for completely resected stage IB to IIIA NSCLC with less common EGFR activating mutations, such as exon 20 insertion?

This episode highlights the significance of third-generation EGFR TKIs in delaying subsequent therapies for resectable, stage IB to IIIA EGFR-mutated NSCLC, explores the risks of postresection treatments for disease progression, and discusses treatment considerations for patients across different stages, focusing on the ADAURA trial outcomes for stage IB to IIIA NSCLC.

This episode discusses the urgent need for more effective and tolerable therapies for patients with EGFR-mutated NSCLC who have exhausted targeted treatments, comparing the clinical benefits of a targeted ADC approach vs chemotherapy, with a focus on the TROPION-Lung01 study of Dato-DXd vs docetaxel for heavily pretreated advanced/metastatic NSCLC with actionable genomic alterations.

This episode covers current sequencing strategies for NSCLC after targeted therapies and platinum chemotherapy, discusses the COMPEL trial with osimertinib, reviews OS and PFS end points from the TROPION-Lung01 study, examines hypotheses behind differential PFS responses in nonsquamous vs squamous NSCLC, and addresses what constitutes a clinically meaningful, durable response in heavily pretreated patients with advanced NSCLC and actionable genomic alterations.

This episode examines the management of ILD/pneumonitis associated with TROP2-directed ADCs in patients with advanced NSCLC and strategies for mitigating these risks, addresses hematologic toxicities related to docetaxel, and discusses the improved tolerability and lower incidence of severe treatment-emergent adverse events with Dato-DXd compared with docetaxel.

This episode discusses the impressive ORR of more than 40% from the phase 2 TROPION-Lung05 trial of Dato-DXd in patients with EGFR-mutated advanced NSCLC, its clinical impact on those treated with 3 or more prior therapies, and explores the potential of Dato-DXd as a practice-changing therapy, given the median DOR of 7 months and DCR of 79%.

This episode addresses strategies for mitigating and managing adverse events associated with Dato-DXd in patients with advanced NSCLC, explores how the drug’s structure may help prevent acquired resistance mechanisms that are common with TKIs, and discusses the broader implications of integrating Dato-DXd and other ADCs into the treatment landscape for this patient population.

This episode reviews the response rates reported in the HERTHENA-Lung01 trial among patients with advanced NSCLC exhibiting various resistance mechanisms, evaluates the clinical significance of responses to HER3-DXd based on HER3 expression scores, discusses the relevance of the reported overall DOR, median PFS, and OS, and examines the CNS ORR among patients with baseline brain metastases in relation to the ORRs.

This episode explores management strategies for hematologic toxicities arising within the first 3 weeks of treatment with HER3-DXd, discusses the potential integration of HER3-DXd into clinical practice upon approval, and identifies unmet needs and suitable patient populations for future clinical trials evaluating HER3-DXd based on insights from the HERTHENA-Lung01 trial results.