An interview with Dr. Ishmael Jaiyesimi from Beaumont Health Royal Oak and Oakland University William Beaumont School of Medicine in Royal Oak, MI, and Dr. Andrew Robinson from Kingston General Hospital, Queen's University in Ontario, Canada, authors on "Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline." Dr. Jaiyesimi and Dr. Robinson review the latest recommendation updates for therapeutic options for patients with stage IV NSCLC with ALK rearrangement or RET rearrangement. They also discuss new agents on the horizon. Read the full guideline at www.asco.org/thoracic-cancer-guidelines.   TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs, covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Ishmael Jaiyesimi from Beaumont Health Royal Oak and Oakland University William Beaumont School of Medicine in Royal Oak, Michigan, and Dr. Andrew Robinson from Kingston General Hospital at Queen's University in Ontario, Canada, authors on 'Therapy for Stage IV Non-small Cell Lung Cancer with Driver Alterations: ASCO Guideline Update'. Thank you for being here, Dr. Jaiyesimi and Dr. Robinson. Dr. Ishmael Jaiyesimi: Thank you. Dr. Andrew Robinson: It’s a pleasure to be here. Brittany Harvey: Great! First, 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 full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Jaiyesimi, do you have any relevant disclosures that are directly related to this guideline? Dr. Ishmael Jaiyesimi: None. Brittany Harvey: Thank you. And, Dr. Robinson, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Andrew Robinson: Yes, I have received funding less than $5,000 from AstraZeneca, Merck, and BMS over the past two years. Brittany Harvey: I appreciate those disclosures. So, then Dr. Jaiyesimi, let's talk about the purpose of this guideline. So, what is the purpose of this guideline update, and what clinical scenarios does this guideline address? Dr. Ishmael Jaiyesimi: The purpose of therapy for stage IV non-small cell lung cancer with driver alterations, is to rapidly update the ASCO and Ontario Health guideline on the systemic treatment of patients with stage IV non-small cell lung cancer, last published in February of 2021. The update is a result of potentially practice-changing evidence published since the last publication in February 2021. The update is based on two clinical trials from 2020 to 2021. The clinical scenario this guideline covers are stage IV non-small cell lung cancer with driver alteration with an ALK gene rearrangement and RET gene rearrangements. Brittany Harvey: Great. So, then let's review those two clinical scenarios that you just mentioned. So, there are a few new recommendations regarding ALK rearrangement. So, what are the recommended first-line options for patients with stage 4 non-small cell lung cancer in an ALK rearrangement? Dr. Ishmael Jaiyesimi: In the previous guideline alectinib or brigatinib were recommended as first-line therapy with a strong recommendation and level of evidence in patients with ALK gene rearrangement, and a performance status of zero to two. In the current update, lorlatinib was cited as the first-line ALK inhibitor that may be offered as an alternative first-line therapy. If alectinib, brigatinib, or lorlatinib are not available, ceritinib or crizotinib should be offered. This is based on the CROWN study that showed alectinib was superior to crizotinib in the fi