Outcome Differences Between First- and Second-generation EGFR Inhibitors in Advanced EGFR Mutated NSCLC in a Large Population-based Cohort
| Autor: | Negar Chooback, Cheryl Ho, Barbara Melosky, S. Lau |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Oncology Adult Male Cancer Research medicine.medical_specialty Lung Neoplasms Afatinib Population Antineoplastic Agents Cohort Studies 03 medical and health sciences Erlotinib Hydrochloride 0302 clinical medicine Gefitinib Internal medicine Carcinoma Non-Small-Cell Lung medicine Humans Lung cancer education Protein Kinase Inhibitors EGFR inhibitors Aged Aged 80 and over education.field_of_study Proportional hazards model business.industry Hazard ratio Middle Aged medicine.disease Survival Analysis respiratory tract diseases ErbB Receptors 030104 developmental biology 030220 oncology & carcinogenesis Mutation Female Erlotinib business medicine.drug |
| Zdroj: | Clinical lung cancer. 20(5) |
| ISSN: | 1938-0690 |
| Popis: | Introduction Second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) appear superior to first-generation TKIs in clinical trials, but at the cost of greater toxicity. It is unclear whether real-world patients, who often suffer worse outcomes, experience similar survival benefits. Using population-based data, we aim to characterize outcome differences by type of treatment. Patients and Methods We reviewed all patients with advanced non–small-cell lung cancer who initiated treatment with an EGFR TKI at BC Cancer between 2010 and 2015. A propensity score was generated to account for imbalances in patient characteristics between treatment groups. A Cox proportional hazards model based on the propensity score was then used to estimate effects of treatment on survival. Results A total of 484 patients were identified for analysis. Patients in the second-generation cohort were younger (62 vs. 67 years), had less baseline central nervous system metastases (9% vs. 22%), and more uncommon EGFR mutations (13% vs. 7%). Patients receiving a second-generation TKI had an improved overall survival (hazard ratio, 0.69; P = .05), driven by the subgroup with an EGFR exon 19 deletion. Patients with a L858R mutation did not appear to derive benefit from a second-generation TKI (hazard ratio, 0.91; P = .74). Overall, 40% of patients receiving a second-generation TKI required a dose reduction, but only 1% required discontinuation. Conclusions Second-generation TKIs tended to be chosen over first-generation TKIs as frontline therapy in younger patients with uncommon EGFR mutations and without central nervous system metastases. The survival benefit of a second-generation TKI seen in clinical trials appeared to be generalizable to real-world patients and is a reasonable first-line therapy. |
| Databáze: | OpenAIRE |
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