Locally advanced/metastatic non-small-cell lung cancer in Lebanon: focus on ALK tyrosine kinase inhibitors
Creators: name: Tfayli, Arafat
name: Ghanem, Hady
name: Nasr, Fadi
name: Kourie, Hampig Raphael
name: Hachem, Georges El
name: Debs, Jamil
name: Masri, Sarah
name: Assi, Hazem I
name: Campelo, Rosario García
name: Kattan, Joseph
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Science Policy
subject: Hematology
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology

description: Treatment of non-small-cell lung cancers (NSCLC) has evolved over the last decade. According to studies, the use of targeted therapies has significantly increased the life expectancy of patients. Moreover, ALK-tyrosine kinase inhibitors (ALK-TKIs) have improved clinical outcomes. In Lebanon, translating recommendations into clinical practice remains challenging. A Lebanese expert panel of oncologists was convened to describe the management paradigm and the clinical evidence supporting the optimal use of next-generation TKIs in patients with <i>ALK</i>-rearranged NSCLC and to provide an expert overview of local challenges and recommendations for optimizing the management of advanced NSCLC in Lebanese patients. The experts agreed that these recommendations should be part of a healthcare strategy to be implemented at the national level. ALK-TKIs: ALK-tyrosine kinase inhibitors NSCLC: Over the last decade, non-small-cell lung cancers (NSCLC) management has evolved and is now based on genetic alterations, including <i>ALK</i> rearrangements. The use of ALK-tyrosine kinase inhibitors (ALK-TKIs) has changed the management paradigm for advanced NSCLC. <b>Diagnosis:</b>○ NGS testing should be preferred over sequential testing to identify several actionable targets, especially in young patients, light smokers, or non-smokers with squamous or mixed histology. NGS testing should be preferred over sequential testing to identify several actionable targets, especially in young patients, light smokers, or non-smokers with squamous or mixed histology. <b>Treatment:</b>○ Due to limitations or unavailability of certain treatments, patients can either be encouraged to enroll in clinical trials or receive a first-generation ALK inhibitor that is always available, instead of a third-generation drug that is extremely potent but may pose a high risk of relapse if given intermittently.○ Panel experts agreed that lorlatinib would be the treatment of choice in patients with brain metastases. In other patients, clinicians would opt for any ALK-TKI. Patients with advanced NSCLC should have a systematic follow-up every 4–6 months, including brain magnetic resonance imaging (MRI).○ Patients who develop drug resistance following ALK-TKI treatment should be offered a rebiopsy or a liquid biopsy.○ MDT-based multimodal approach should be implemented for the management of NSCLC. Due to limitations or unavailability of certain treatments, patients can either be encouraged to enroll in clinical trials or receive a first-generation ALK inhibitor that is always available, instead of a third-generation drug that is extremely potent but may pose a high risk of relapse if given intermittently. Panel experts agreed that lorlatinib would be the treatment of choice in patients with brain metastases. In other patients, clinicians would opt for any ALK-TKI. Patients with advanced NSCLC should have a systematic follow-up every 4–6 months, including brain magnetic resonance imaging (MRI). Patients who develop drug resistance following ALK-TKI treatment should be offered a rebiopsy or a liquid biopsy. MDT-based multimodal approach should be implemented for the management of NSCLC. <b>Managing toxicity:</b>○ Most adverse events resolve without any intervention. For grade I adverse events (AEs), neither dose reduction nor withholding treatment is necessary. However, for grade II or above AEs, the dose should be reduced and in cases where a severe AE re-occurs, treatment must be stopped and the patient monitored for recovery. For cognitive dysfunction, physicians should rule out any potential causes of Central nervous system (CNS) impairment before attributing it to lorlatinib treatment. Most adverse events resolve without any intervention. For grade I adverse events (AEs), neither dose reduction nor withholding treatment is necessary. However, for grade II or above AEs, the dose should be reduced and in cases where a severe AE re-occurs, treatment must be stopped and the patient monitored for recovery. For cognitive dysfunction, physicians should rule out any potential causes of Central nervous system (CNS) impairment before attributing it to lorlatinib treatment. Several challenges are currently affecting Lebanese practice, including a deteriorating healthcare system, limited access to biomarker testing, high costs associated with diagnosis and treatment and shortages in medication and equipment.