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Introduction: Treatment paradigms for -mutated non-small cell lung cancer (NSCLC) have successfully evolved since the introduction of osimertinib. The detection of T790M mutation in plasma or tumor samples obtained at disease progression to first-/second-generation EGFR inhibitors is mandatory for osimertinib prescription. Nevertheless, pharmacokinetics properties of osimertinib guarantee its usefulness in central nervous system (CNS) disease even in the case of T790M-negative or unknown status.
Patients And Methods: In this brief report, we share the clinical histories of two patients with CNS-preeminent progression under first-/second-generation EGFR inhibitors in which it was not possible to document the presence of T790M resistance mutation.
Results: Patient outcomes diverged dramatically due to the differential availability of off-label osimertinib.
Conclusions: Waiting for the novel molecule to be approved and licensed in first-line treatment, our report of hope and frustration is intended to stress the opportunity of its administration in the case of CNS failure of first-line EGFR inhibition, even in the absence of T790M proof.
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http://dx.doi.org/10.1177/0300891618809826 | DOI Listing |
Front Immunol
September 2025
Department of Thoracic Surgery, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, China.
Background: Lung cancer remains the leading cause of cancer-related mortality globally, primarily due to late-stage diagnosis, molecular heterogeneity, and therapy resistance. Key biomarkers such as EGFR, ALK, KRAS, and PD-1 have revolutionized precision oncology; however, comprehensive structural and clinical validation of these targets is crucial to enhance therapeutic efficacy.
Methods: Protein sequences for EGFR, ALK, KRAS, and PD-1 were retrieved from UniProt and modeled using SWISS-MODEL to generate high-confidence 3D structures.
J Immunother Precis Oncol
August 2025
Department of Medical Oncology, Sir H N Reliance Foundation Hospital and Research Centre, Mumbai, India.
Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC) with limited treatment options and poor prognosis. mutations generally respond to tyrosine kinase inhibitors (TKIs)-based targeted therapy but are typically associated with resistance to immunotherapy. We report a case of oligometastatic PSC harboring compound mutations (p.
View Article and Find Full Text PDFJ Immunother Precis Oncol
August 2025
Tawam Hospital, AlAin, UAE.
Over the past decade, the discovery of immunotherapy and targeted therapy has set new standards for the management of advanced non-small cell lung cancer (NSCLC). This study aims to investigate the prevalence of , , , , , , and mutations in patients with NSCLC within the Middle East and North Africa (MENA) region and to assess the current state of molecular testing and targeted treatments in the Gulf Cooperation Council (GCC) region. The systematic literature review was performed using PubMed, Google Scholar, and Google searches to identify studies on the prevalence of , , , , , , and mutations in patients with NSCLC in the MENA region.
View Article and Find Full Text PDFZhonghua Jie He He Hu Xi Za Zhi
September 2025
Department of nursing, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are important treatments for EGFR mutant non-small cell lung cancer (NSCLC). However, the first and second generation EGFR-TKI face clinical limitations due to acquired resistance, such as the T790M mutation. Irreversible EGFR-TKI can significantly prolong the survival of patients by enhancing the inhibition of drug-resistant mutations through the covalent binding mechanism.
View Article and Find Full Text PDFJ Thorac Oncol
September 2025
Institut du Thorax Curie-Montsouris, Paris, France; Paris-Saclay University, UVSQ-Versailles, France.
Introduction: Amivantamab plus lazertinib significantly improved progression-free and overall survival versus osimertinib in patients with previously untreated, EGFR-mutant advanced NSCLC. EGFR-targeted therapies are associated with dermatologic adverse events (AEs), which can affect quality of life (QoL). COCOON was conducted to assess prophylactic management and improve treatment experience.
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