Dr. Natash Leighl and Dr. Jyoti Patel are back on the podcast to discuss the update to the living guideline on stage IV NSCLC with driver alterations. This guideline includes recommendations for first-, second-, and subsequent-line therapy for patients with driver alterations including: EGFR, ALK, ROS1, BRAFV600E, MET exon skipping mutation, RET rearrangement, NTRK rearrangement, HER2, and KRAS G12C. They highlight the key changes to the recommendations, addition of recent trials, the importance of biomarker testing, and the impact of this guideline for clinicians and patients living with advanced NSCLC. Stay tuned for future updates to this continuously updated guideline. Read the full update, “Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3” at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.02744.    Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.    My name is Brittany Harvey, and today I am interviewing Dr. Jyoti Patel and Dr. Natasha Leighl, co-chairs on “Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3.” Thank you for being here, Dr. Patel and Dr. Leighl.  And before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Patel and Dr. Leighl, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So, to start us off on this living clinical practice guideline, Dr. Leighl, this guideline for systemic therapy for patients with stage four non-small cell lung cancer with driver alterations is being routinely updated. What new data was reviewed in this full update to the living guideline? Dr. Natasha Leighl: Thanks so much, Brittany. So, we looked through the literature for publications between February and the end of October 2023, and also any novel agents that were approved, in particular by the United States FDA, to really incorporate this update in the current guidelines. In particular, we had updates in EGFR-driven tumors, BRAF and RET-driven tumors. And we also worked very hard to make this more digestible. In particular, it was turning into a bit of a laundry list of all of the things that we had ever recommended. So we really wanted to shorten things, pare them down, and really make them helpful and very, very current for the treatment of people with lung cancer in 2023 and 2024. Brittany Harvey: Excellent. Thank you for providing that overview of the evidence reviewed and the key updates that we will address in this guideline. So then I would like to talk about some of those key updated recommendations from the expert panel. You mentioned both EGFR, BRAF, and RET. So starting with patients with stage IV non-small cell lung cancer with EGFR alterations, Dr. Leighl, what are the key changes to those recommendations? Dr. Natasha Leighl: So, as I said, we really started to get quite a long list of things we recommended, including drugs that, to be honest, we no longer think are what we should lead with first-line. So we updated the recommendation to recommend first-line osimertinib in patients with sensitizing mutations. We were also able to capture in this upd