Mechanisms of Resistance to First-Line Osimertinib in Hispanic Patients With EGFR Mutant Non-Small Cell Lung Cancer
Andrés F Cardona1, Alejandro Ruiz-Patiño2, Gonzalo Recondo3
1Direction of Research and Education, Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC), Bogotá, Colombia; Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá, Colombia; Molecular Oncology and Biology Systems Research Group (Fox-G/ONCOLGroup), Universidad El Bosque, Bogotá, Colombia.
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.
Insights
First-line Osimertinib is effective and safe for Hispanic patients with non-small cell lung cancer (NSCLC). Liver metastases and high tumor mutational burden were linked to reduced progression-free survival (PFS).
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Osimertinib is a third-generation EGFR-TKI for advanced non-small cell lung cancer (NSCLC).
- Limited data exists on Osimertinib's effectiveness in Hispanic populations.
- This study addresses the gap in understanding real-world outcomes for Hispanic NSCLC patients.
Purpose of the Study:
- To evaluate the real-world effectiveness and safety of first-line Osimertinib in Hispanic patients with NSCLC.
- To analyze post-progression outcomes in this specific demographic.
- To identify factors influencing progression-free survival (PFS).
Main Methods:
- Multicenter, multinational, retrospective cohort study.
- Included 94 Hispanic patients with metastatic EGFR-mutated NSCLC receiving first-line Osimertinib.
- Assessed PFS and post-progression survival; utilized NGS for resistance mutations.
Main Results:
- Median PFS was 14.4 months; median post-progression survival was 7.73 months.
- Liver metastases and tumor mutational burden > 5 mut/Mb negatively impacted PFS.
- Common progression sites included lung/pleura and lymph nodes.
Conclusions:
- First-line Osimertinib is an effective and safe treatment for Hispanic patients with metastatic NSCLC.
- Liver metastases and higher tumor mutational burden are associated with reduced PFS.
- Mechanisms of resistance were identified, some targetable by other therapies.
More Related Videos
Related Concept Videos
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...