Patients with advanced non-small cell lung cancer are eligible for first-line treatment with osimertinib, a third-generation EGFR-TKI inhibitor (NSCLC). In addition, it is the treatment of choice for people who have T790M mutations and show signs of illness progression or deterioration. Despite the extensive research on the drug’s efficacy and safety in clinical trials and observational studies, data on the outcomes of Osimertinib treatment in Hispanic patients is limited. That study aimed to evaluate the efficacy and safety of first-line Osimertinib in a population of Hispanic patients with NSCLC, focusing on outcomes following disease progression. Hispanic individuals with EGFR-mutated NSCLC are the focus of this retrospective cohort study conducted at multiple sites across the globe. Researchers found that patients with metastatic EGFR-mutated NSCLC were identified and enrolled if they received Osimertinib (80mg/day until evidence of disease progression or severe adverse effects). Those individuals with disease progression had tumor samples, or liquid biopsies analyzed using NGS. Progression-free survival was the primary endpoint, with overall survival after progression as an additional endpoint. The median age was 59 years old among 94 patients from the United States of America, Mexico, Argentina, Costa Rica, Colombia, Panama, and Chile who participated. Both EGFR Exon 19 deletions and EGFR pL858R point mutations were found. The 95% CI for the median progression-free survival (PFS) was 14.4 months. The most frequent metastatic sites were the lungs/pleura and lymph nodes. The median time to death after progression was 7.73 months (95% CI, 4.07-9.85). The existence of liver metastases at diagnosis and a tumor mutational burden of more than 5 mut/Mb were factors that reduced PFS. Many individuals in this cohort developed resistance despite the treatment’s efficacy, and several mechanisms of resistance were identified, including mutations that can be addressed by other therapies.