Dr Herzberg on the Expanding Toolkit in KRAS-Mutant Non–Small Cell Lung Cancer

In this episode of Targeted Talks, Benjamin Herzberg, MD, discusses the evolving treatment landscape for KRAS-mutant non–small cell lung cancer (NSCLC). He explains why KRAS matters to all oncologists, since these mutations drive roughly 30% of NSCLC cases, and reviews why chemoimmunotherapy remains the first-line standard of care for now. He also covers how central nervous system metastases affect treatment planning and why close collaboration with pathology and upfront biomarker testing are essential. Herzberg then turns to the pan-RAS inhibitor daraxonrasib (Rasonque), recently approved in pancreatic cancer, and explains why lung cancer clinicians should pay attention. He discusses its published lung cancer data, which show response rates and durability similar to those in pancreatic cancer, as well as the ongoing phase 3 trial vs docetaxel. He also discusses zoldonrasib, a G12D-specific inhibitor with a favorable tolerability profile, and the idea of a "RAS toolkit" of pan-RAS and allele-specific agents. He closes with the biggest unmet needs, including driver-negative disease and resistance to targeted therapy, and what excites him most: molecular glues and other novel drug modalities, including MTAP/PRMT5 inhibitors.

00:00 Introduction to KRAS-Mutant Lung Cancer
00:40 Prevalence and Variants of KRAS Mutations
01:41 First-Line Chemoimmunotherapy for KRAS NSCLC
03:15 Managing CNS Metastases in Lung Cancer
05:11 Upfront Biomarker Testing and Collaboration
08:05 Adagrasib's Role in KRAS-Mutant Lung Cancer
10:22 Unmet Needs and Resistance Mechanisms
12:31 Future of RAS Inhibitors and the RAS Toolkit