Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer (FRESTON-CLICaP)

• Published in: Clinical lung cancer Vol. 23; no. 6; pp. 522 - 531
• Main Authors: Cardona, Andrés F., Ruiz-Patiño, Alejandro, Recondo, Gonzalo, Martín, Claudio, Raez, Luis, Samtani, Suraj, Minatta, José Nicolas, Blaquier, Juan Bautista, Enrico, Diego, Burotto, Mauricio, Ordóñez-Reyes, Camila, Chamorro, Diego F., Garcia-Robledo, Juan Esteban, Corrales, Luis, Zatarain-Barrón, Zyanya Lucia, Más, Luis, Sotelo, Carolina, Ricaurte, Luisa, Santoyo, Nicolas, Cuello, Mauricio, Mejía, Sergio, Jaller, Elvira, Vargas, Carlos, Carranza, Hernán, Otero, Jorge, Rodríguez, July, Archila, Pilar, Bermudez, Maritza, Gamez, Tatiana, Cordeiro de Lima, Vladmir, Freitas, Helano, Russo, Alessandro, Polo, Carolina, Malapelle, Umberto, Perez, Diego de Miguel, Rolfo, Christian, Viola, Lucia, Rosell, Rafael, Arrieta, Oscar
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2022
• Subjects: Carcinoma; Drug resistance; EGFR mutations; Non-Small-Cell Lung Cancer; Osimertinib; Osimertinib; EGFR mutations; Carcinoma; Non-Small-Cell Lung Cancer; Drug resistance
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2022.06.001

•Our study is the first real-world analysis of Osimertinib in the first line setting in Hispanic patients and post-progression results.•Osimertinib is an effective therapy in treating Hispanic patients with EGFR-non-small cell lung cancer in the first-line setting.•Despite Osimertinib effectiveness, cancer cells develop resistance mechanisms, allowing several patients to relapse.•When in progression, patients with liver metastases present with worse survival outcomes. Osimertinib is a third generation EGFR-TKI inhibitor approved in the first-line setting for patients with advanced non-small cell lung cancer (NSCLC). Additionally, it represents the treatment of choice in patients who present with T790M mutations and evidence of relapse of the disease. Effectiveness and safety of this drug have been studied in multiple clinical trials and observational studies, however, information regarding outcomes among Hispanic patients treated with Osimertinib is scarce. The objective of this study was to examine real-world effectiveness and safety of first-line Osimertinib in a cohort of Hispanic patients with NSCLC, emphasizing post-progression outcomes. This is a multicenter, multinational, retrospective cohort study of Hispanic patients treated with Osimertinib as first-line for EGFR-mutated NSCLC. Patients with a confirmed diagnosis of metastatic EGFR-mutated NSCLC who received Osimertinib (80mg/day until evidence of disease progression or presence of intolerable adverse effects) were identified and included. NGS was performed in tumor samples or liquid biopsies among patients who had disease progression. The primary outcome was progression-free survival, and the secondary outcome was post-progression survival. A total of 94 patients from Mexico, Argentina, Costa Rica, Colombia, Panama, Chile and the USA were included, with a median age of 59 years. Identified mutations included EGFR Exon 19 deletions and EGFR pL858R point mutations. Median progression-free survival (PFS) was 14.4 months (95%CI 12.4–18.2 months). Lung/pleura and lymph nodes were the most common sites of progression. Median post-progression survival was 7.73 months (95%CI 4.07 months-Not reached). Factors which negatively affected PFS included presence of liver metastases at diagnosis and a tumor mutational burden > 5 mut/Mb. Treatment with first line osimertinib represents an effective and safe option for Hispanic patients with metastatic NSCLC. Liver metastases and a higher tumor mutation burden were associated with a lower PFS. Despite effectiveness, different mechanisms of resistance were identified among the patients in this cohort, including mutations which can be targeted by other therapeutic options. This is a real-world data analysis of Osimertinib in the first line setting for Hispanic patients with Non-Small Cell Lung Cancer. We performed a multicenter retrospective cohort study with patients with a diagnosis of NSCLC and EGFR sensitizing mutation. We found that among Hispanics, Osimertinib is an effective and safe treatment option as first-line therapy. Besides its effectiveness, there are several molecular resistance mechanisms that should be analyzed.