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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalClinical Lung Cancer
DOIs
StateAccepted/In press - 2022
Externally publishedYes

Bibliographical note

Funding Information:
Andrés F. Cardona discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, and The Foundation for Clinical and Applied Cancer Research – FICMAC. Additionally, he was linked and received honoraria as an advisor, participated in speakers' bureau, and gave expert testimony to Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, and Foundation for Clinical and Applied Cancer Research – FICMAC. Oscar Arrieta reports personal fees from Pfizer, grants and individual fees from Astra Zeneca, grants, and individual fees from Boehringer-Ingelheim, personal fees from Lilly, individual fees from Merck, personal fees from Bristol Myers Squibb, grants, and personal fees from Roche, outside the submitted work. Gonzalo Recondo reports personal fees from Pfizer, Roche, Amgen, Bayer, Takeda, MSD, Merck Serono, research grants from Amgen and Janssen, outside of the submitted work. Juan Blaquier has nothing to disclose.

Funding Information:
Supported by The CLICaP and The Foundation for Clinical and Applied Cancer Research- FICMAC (Bogotá, Colombia) research grant 023-2019 .

Publisher Copyright:
© 2022

Keywords

  • Carcinoma
  • Drug resistance
  • EGFR mutations
  • Non-Small-Cell Lung Cancer
  • Osimertinib

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