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Singhi1 · Eric S. Nadler2  \nReceived: 11 July 2025 / Accepted: 2 December 2025 / Published online: 28 January 2026 © The Author(s) 2026, modified publication 2026  \nAbstract  \nThe podcast discusses the available treatment options for patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) and focuses on the efficacy and safety of first-line treatments and sequencing strategies. Patients with ALK-positive NSCLC often need multiple lines of therapy owing to the development of resistance, disease progression, brain metastases, or adverse events. Several options are available for the treatment ofALK-positive NSCLC; therefore, it is important to make an informed decision on which treatment to use in the first line. The podcast also discusses the challenges in treatment sequencing due to high attrition rates from first-line to second-line therapy and the decline in treatment efficacy with each additional line. Real-world data indicate that many patients do not receive second-line therapy after discontinuing first-line treatment. The discussion emphasizes the importance of consideration of drug efficacy, safety outcomes, potential treatment resistance, and development of brain metastases when determining treatment strategies. Ultimately, it is essential to select the best treatment first and proactively manage any potential adverse events to ensure that patients can derive clinical benefit and safely remain on therapy.  \nThe podcast and transcript can be viewed below the abstract of the online version of the manuscript. Alternatively, the podcast can be downloaded here: [https://doi.org/10.6084/m9.figshare.30762473](https://doi.org/10.6084/m9.figshare.30762473) .  \n\n|  |\n| --- |\n| Key Points |\n| Several first-line treatment options are currently available for patients with ALK-positive metastatic NSCLC. |\n| The risk–benefit profile of each treatment option should be assessed and discussed with patients before starting treatment. |\n| Supplementary file2 (MP4 190240 KB) |\n\n* Eric K. Singhi [EKSinghi@mdanderson.org](EKSinghi@mdanderson.org)  \n1 The University of Texas MD Anderson Cancer Center, Houston, TX, USA  \n2 Baylor University Medical Center, Dallas, TX, USA  \nTranscript  \nEric Singhi, MD (ES): Thoracic and Head & Neck Medical Oncologist and Assistant Professor at The University of Texas MD Anderson Cancer Center  \nEric Nadler, MD, MPP (EN): Medical Director of US Oncology Health Informatics and Internet Technology at Baylor University Medical Center  \n1 Introduction  \nES: Hello, and welcome to the podcast. My name is Dr. Eric Singhi, and I am a Thoracic and Head & Neck Medical Oncologist and Assistant Professor at The University of Texas MD Anderson Cancer Center.  \nEN: Hello, my name is Eric Nadler, and I’m the Medical Director of Health Outcomes at Baylor University Medical Center and a head and neck and lung cancer doctor there as well.  \nIn today’s podcast, which is being hosted in the journal Targeted Oncology, we discuss the use of first-line treatments in patients with anaplastic lymphoma kinase–positive, or ALK-positive, metastatic non-small cell lung cancer (NSCLC) . We will provide an overview of the guidelines for first-line treatment and discuss the clinical trials and evidence of efficacy and safety supporting these first-line  \ntreatment options, sequencing strategies, patient attrition from the first line to the second line, and the appropriate treatment based on the available data.  \n2 EN: Eric, can you provide us  \nwith an overview ofALK‑positive NSCLC?  \nES: Sure! So NSCLC, it accounts for approximately 85% of all lung cancers and is the leading cause of cancer deaths worldwide [1] .  \nALK-positive NSCLC represents 3–5% of all NSCLC case","cbCaibO4jvip85e6","https://ap.wps.com/l/cbCaibO4jvip85e6","pdf",631486,"English","# Key Points\n## Several first-line treatment options\n## Risk–benefit assessment\n## Supplementary file\n# Transcript\n## Introduction\n## Overview of ALK-positive NSCLC\n## Current guidelines for first-line treatment","[{\"question\":\"What patient factors make treatment sequencing important in ALK-positive metastatic NSCLC?\",\"answer\":\"ALK-positive NSCLC often leads to resistance, disease progression, brain metastases, and adverse events, which can force multiple therapy lines. Sequencing matters because treatment benefit may decline with each subsequent line.\"},{\"question\":\"Why are brain metastases a major issue in ALK-positive NSCLC management?\",\"answer\":\"Brain metastases have higher baseline and cumulative incidences than many other oncogene-driven diseases. They worsen prognosis, and the intracranial response can influence treatment selection.\"},{\"question\":\"How should clinicians and patients decide on a first-line therapy?\",\"answer\":\"The discussion emphasizes evaluating the risk–benefit profile of each option together with patients. Decisions should consider drug efficacy, safety outcomes, potential resistance, and the likelihood of brain metastasis.\"}]","First Things First - Navigating ALK-Positive Metastatic Non-Small Cell Lung Cancer Treatment Options - A Podcast | PDF",1790125883,18]