Observational studyTargeted oncology2023
Genomic Landscape of Primary Resistance to Osimertinib Among Hispanic Patients with EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC): Results of an Observational Longitudinal Cohort Study.
Observational study in Targeted oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- The impact of EGFR T790M mutation status following the development of Osimertinib resistance on the efficacy of Osimertinib in non-small cell lung cancer: A meta-analysis.The clinical respiratory journal · 2024Pooled it
- Predicting primary resistance to third-generation EGFR-TKIs in lung adenocarcinoma using a multisource cross-modal transformer model.NPJ precision oncology · 2026Article
- Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC - mechanisms and evolving treatment approaches.Nature reviews. Clinical oncology · 2026Review
- Review
- Actionable mutations and targeted therapy in non-small cell lung cancer among Latin American and Hispanic patients: a systematic literature review of prognosis and meta-analysis.Translational lung cancer research · 2025Article
- Spatial Heterogeneity of PD-L1 Expression as a Biomarker for Third-Generation EGFR-TKI Response in Advanced EGFR-Mutant NSCLC.Cancer science · 2025Article
- Analysis of genomic alternations in epidermal growth factor receptor (EGFR)-T790M-mutated non-small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Optimizing Osimertinib for NSCLC: Targeting Resistance and Exploring Combination Therapeutics.Cancers · 2025Review
- Allosteric ligand-driven smart nanoconjugates for mutation-selective EGFR targeting: A precision approach to overcoming tyrosine kinase inhibitor resistance.BioImpacts : BI · 2025Review
- Cancer genomics and bioinformatics in Latin American countries: applications, challenges, and perspectives.Frontiers in oncology · 2025Review
- A meta-analysis of liquid biopsy versus tumor histology for detecting EGFR mutations in non-small cell lung cancer.Translational oncology · 2024Article
- Epidermal growth factor receptor-mutated lung carcinomas with insufficient response to epidermal growth factor receptor inhibitors.Future oncology (London, England) · 2024Review
- Intrinsic Resistance to Osimertinib in EGFR Mutated NSCLC Cell Lines Induced by Alteration in Cell-Cycle Regulators.Targeted oncology · 2023Article
- Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non-small cell lung cancer.Thoracic cancer · 2023Review
- Long-lasting benefit on multimodal treatment combining osimertinib and stereotaxic radiotherapy for metastatic non-small cell lung cancer with the EGFR exon 20 insertion 773-774 HVdelinsLM: a case report.Frontiers in oncology · 2023Article
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Authors and funding
38 authors at 16 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpidermal growth factor receptor (EGFR) mutations (EGFRm) represent one of the most common genomic alterations identified among patients with non-small cell lung cancer (NSCLC). Several targeted agents for patients with EGFRm have been proven safe and effective, including the third-generation tyrosine kinase inhibitor (TKI) osimertinib. Nonetheless, some patients will present with or develop EGFR-TKI resistance mechanisms.
objectiveWe characterized the genomic landscape of primary resistance to osimertinib among Hispanic patients with EGFR-mutant NSCLC.
methodsAn observational longitudinal cohort study was conducted with two groups of patients, those with intrinsic resistance (cohort A) and those with long-term survival (cohort B). All patients were treated and followed between January 2018 and May 2022. All patients were assessed for Programmed Cell Death Ligand 1 (PD-L1) expression and Bcl-2-like protein 11 (BIM)/AXL mRNA expression before starting TKI. After 8 weeks of treatment, a liquid biopsy was performed to determine the presence of circulating free DNA (cfDNA), and next-generation sequencing (NGS) was used to identify mutations at the time of progression. In both cohorts, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated.
resultsWe found a homogeneous distribution of EGFR-sensitizing mutations in both cohorts. For cohort A, exon 21 mutations were more common than exon 19 deletions (ex19dels) for cohort B (P = 0.0001). The reported ORR for osimertinib was 6.3% and 100% for cohorts A and B, respectively (P = 0.0001). PFS was significantly higher in cohort B (27.4 months vs. 3.1 months; P = 0.0001) and ex19del patients versus L858R (24.5 months, 95% confidence interval [CI] 18.2-NR), vs. 7.6 months, 95% CI 4.8-21.1; P = 0.001). OS was considerably lower for cohort A (20.1 months vs. 36.0 months; P = 0.0001) and was better for patients with ex19del, no brain metastasis, and low tumor mutation burden. At the time of progression, more mutations were found in cohort A, identifying off-target alterations more frequently, including TP53, RAS, and RB1.
conclusionEGFR-independent alterations are common among patients with primary resistance to osimertinib and significantly impact PFS and OS. Our results suggest that among Hispanic patients, other variables associated with intrinsic resistance include the number of commutations, high levels AXL mRNA, and low levels of BIM mRNA, T790M de novo, EGFR p.L858R presence, and a high tumoral mutational burden.
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