Dr. Jyoti Patel and Dr. Natasha Leighl discuss the latest full update to the stage IV NSCLC without driver alterations living guideline. This guideline addresses first-, second-, and subsequent-line therapy for patients according to their histology (squamous cell and nonsquamous cell carcinomas) and PD-L1 expression. They discuss the streamlined recommendations, incorporation of recent evidence, and the highlights for implementation of these recommendations in the treatment of advanced non-small lung cancer. Dr. Patel and Dr. Leighl also point out ongoing trials that will inform this continuously updated guideline as we look ahead.  Read the full update, “Therapy for Stage IV Non-Small-Cell Lung Cancer Without 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.23.02746.    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 of our shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Jyoti Patel and Dr. Natasha Leighl, co-chairs on “Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.3.” Thank you for being here, Dr. Patel and Dr. Leighl. Before we discuss this guideline, I'd 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 the content of this episode, Dr. Patel, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer without driver alterations is being updated on a regular basis. Could you provide some background information on the process for these living guidelines? Dr. Jyoti Patel: The ASCO Living Guideline offers continually updated recommendations based on review of systemic randomized controlled trials. We bring a panel of experts together that includes representatives from Ontario Health as well as ASCO patient representatives. We review phase III studies and other published studies between the times from July 2022 and October 2023 for this most updated guideline. We think about the size of the populations that are being tested, what kind of interventions we have, the outcomes. We certainly look at PFS, as well as OS, but also toxicity, and overall response rates. We prioritize randomized trials and really look for studies that have large sample sizes. We exclude studies that were only meeting abstracts and really look at those that are published in peer-reviewed journals.  When we weigh the evidence, we really think about a number of factors. So what is the strength of the evidence, what’s the sample size, and how we can make recommendations for our patients based on the totality of the data. Certainly, because this is such a rapidly evolving field, one of the things we are looking at is how to update in real-time these guidelines. So for this coming year, for example, these guidelines are published and we look forward to quarterly updates and, again, incorporate the latest evidence. Brittany Harvey: Great. Thank you for that explanation on the background and how these living guidelines are developed.  So, Dr