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

Dr. Mauricio Cuello
Dr. Andrés F Cardona
Dr. Alejandro Ruiz-Patiño
Dr. Gonzalo Recondo
Dr. Claudio Martín
Dr. Luis Raez
Dr. Suraj Samtani
Dr. José Nicolas Minata
Dr. Juan Bautista Blaquier
Dr. Diego Enrico
Dr. Mauricio Burotto
Dra. Camila Ordóñez-Reyes
Dr. Diego F Chamorro
Dr. Juan Esteban Garcia-Robledo
Dr. Luis Corrales
Dr. Zyanya Lucia Zatarain-Barrón
Dr. Luis Más
Dra. Carolina Sotelo
Dra.Luisa Ricaurte
Dr. Nicolas Santoyo
Dr. Sergio Mejía
Dra. Elvira Jaller
Dr. Carlos Vargas
Dr. Hernán Carranza
Dr. Jorge Otero
Dr. July Rodríguez
Dra. Pilar Archila
Dra. Maritza Bermudez
Dra. Tatiana Gamez
Dr. Vladmir Cordeiro de Lima
Dr. Helano Freitas
Dr. Alessandro Russo
Dra. Carolina Polo
Dr. Umberto Malapelle
Dr. Diego de Miguel Perez
Dr. Christian Rolfo
Dra. Lucia Viola
Dr. Rafael Rosell
Dr. Oscar Arrieta


Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Carcinoma; Drug resistance; EGFR mutations; Non-Small-Cell Lung Cancer; Osimertinib.