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Optimizing Treatment Strategies for Egfr-Mutated Non-Small-Cell Lung Cancer Treated with Osimertinib: Real-World
Quentin Dominique Thomas1, Nicolas Girard2, Lise Bosquet3
1Department of Medical Oncology, Institut du Cancer de Montpellier, 34000 Montpellier, France.
Abstract:
Background: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), demonstrated superior efficacy over first-generation TKIs in the FLAURA trial, resulting in its approval as first-line therapy for metastatic non-small-cell lung cancer (NSCLC). However, the real-world application of these trial results requires an evaluation of sequential therapeutic strategies. Methods: This retrospective, non-interventional study utilized data from the Epidemiological Strategy and Medical Economics (ESME) platform, which includes information on patients treated for lung cancer since 2015. Out of 39,974 patients in the database, 624 patients with EGFR-mutant advanced NSCLC treated with osimertinib as first-line (L1, n = 198) or second-line (L2, n = 426) treatment after first- or second-generation TKIs (n = 1262) were identified. Patient demographics, disease characteristics, treatment strategies, and disease progression were examined. Survival analyses were performed using Kaplan-Meier estimates and Cox proportional-hazards models. Results: In the study population (n = 624), 73.4% were female, with a median age of 70 years (range 28-93). Brain metastases at the start of osimertinib treatment were observed in 282 patients. ECOG PS-2 was reported in 29.4% of patients. The T790M mutation in exon 20 was identified in 257/426 patients (60.3%) receiving osimertinib in L2. Median progression-free survival (PFS) was 12.4 months (95% CI [10.7-14.7]) for L1 and 7.4 months (95% CI [6.2-8.7]) for L2. Median overall survival (OS) from advanced diagnosis was 28.5 months (95% CI [26.3-38.7]) for osimertinib L1 and 29.9 months (95% CI [28.6-31.8]) for osimertinib L2 (HR = 0.93; 95% CI [0.75-1.16]; p = 0.50). For L1, median OS was 27.1 months (95% CI [22.0-30.2]) for patients with cerebral metastases and 38.7 months (95% CI [26.3-52.8]) for those without (HR = 0.73; 95% CI [0.48-1.11]; p = 0.15). Discussion: Patients in the real-world ESME database exhibited a poorer prognosis compared to those in the FLAURA trial. The presence of cerebral metastases at diagnosis worsens the prognosis.
Insights
Osimertinib shows similar overall survival whether used as first- or second-line therapy for EGFR-mutant NSCLC in real-world data. However, brain metastases at diagnosis negatively impact prognosis, highlighting the need for effective sequential treatment strategies.
Area of Science:
- Oncology
- Pharmacology
- Epidemiology
Background:
- Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is approved for first-line treatment of metastatic non-small-cell lung cancer (NSCLC).
- Real-world data is needed to evaluate sequential therapeutic strategies involving osimertinib.
- The FLAURA trial demonstrated osimertinib's superior efficacy over first-generation TKIs.
Purpose of the Study:
- To evaluate the real-world effectiveness of osimertinib as a first-line (L1) or second-line (L2) treatment in patients with EGFR-mutant advanced NSCLC.
- To compare survival outcomes between L1 and L2 osimertinib treatment strategies.
- To identify factors influencing prognosis in this patient population.
Main Methods:
- Retrospective, non-interventional study using the ESME platform (data since 2015).
- Identified 624 patients with EGFR-mutant advanced NSCLC treated with osimertinib (198 L1, 426 L2).
- Analyzed demographics, disease characteristics, treatment strategies, and survival using Kaplan-Meier and Cox models.
Main Results:
- Median progression-free survival (PFS) was 12.4 months for L1 and 7.4 months for L2.
- Median overall survival (OS) was comparable: 28.5 months for L1 and 29.9 months for L2 (HR=0.93, p=0.50).
- Brain metastases at diagnosis were associated with a worse prognosis in L1 patients (median OS 27.1 vs. 38.7 months).
Conclusions:
- Real-world outcomes in the ESME database suggest similar overall survival for osimertinib in L1 versus L2 settings.
- Patients in this real-world cohort had a poorer prognosis than those in the FLAURA trial.
- The presence of brain metastases at diagnosis significantly worsens prognosis, underscoring the need for optimized sequential treatment approaches.
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