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Published on: November 22, 2021
Overall Survival in EGFR-Mutant Advanced NSCLC Treated With First-Line Osimertinib: A Cohort Study Integrating
Joshua K Sabari1, Helena A Yu2, Parthiv J Mahadevia3
1Perlmutter Cancer Center, New York University Langone Health, New York, New York.
Introduction:
Patients with NSCLC harboring EGFR mutations (EGFRm) have high mortality. The third-generation tyrosine kinase inhibitor, osimertinib, is approved for first-line EGFRm NSCLC. We used longitudinal U.S. medical oncology databases to evaluate real-world overall survival (rwOS) and prognostic risk factor groups in advanced EGFRm NSCLC treated with first-line osimertinib.
Methods:
This retrospective, new-user cohort study used electronic records from ConcertAI, Flatiron Clinical-Genomics, and COTA databases. Patients with advanced or metastatic EGFRm NSCLC initiating osimertinib monotherapy in first line between April 1, 2018, and October 30, 2022, were included. Follow-up was until death or October 31, 2023. rwOS was estimated using the Kaplan-Meier method. Risk factors were evaluated using multivariate analysis.
Results:
A total of 1323 patients were included with a median follow-up of 20 months. Median age was 70 (range 35-89) years. Median rwOS was 28.6 months (95% confidence interval 26.8-30.9). In high-risk subgroups, median rwOS (mo) was 18.1 in patients with Eastern Cooperative Oncology Group score greater than or equal to 2, 24.3 with brain metastases, 19.3 with liver metastases, and 25.7 with TP53 co-mutation. In total, 95% of patients had at least one high-risk factor. Prevalence of Eastern Cooperative Oncology Group greater than or equal to 2 was 17%, brain metastases 36%, liver metastases 15%, and TP53 co-mutation 63%. Risk of death was significantly higher in patients with high-risk factors (p ≤ 0.011 for all). In total, 58% of patients survived to 2 years, 18% to 5 years, and 33% did not receive second-line therapy.
Conclusion:
Despite advances in tyrosine kinase inhibitor treatments, long-term survival of patients with advanced EGFRm NSCLC remains poor. Nearly all patients had risk factors for mortality and one-third did not receive second-line therapy.
Insights
Real-world survival for advanced EGFR-mutated non-small cell lung cancer (NSCLC) patients on first-line osimertinib remains poor, with nearly all patients having mortality risk factors. One-third did not receive subsequent therapy, highlighting unmet needs in treatment.
Area of Science:
- Oncology
- Clinical Research
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) with EGFR mutations (EGFRm) is associated with high mortality.
- Osimertinib, a third-generation tyrosine kinase inhibitor, is approved for first-line treatment of advanced EGFRm NSCLC.
- Real-world data is crucial for understanding treatment outcomes and identifying prognostic factors.
Purpose of the Study:
- To evaluate real-world overall survival (rwOS) in patients with advanced EGFRm NSCLC receiving first-line osimertinib.
- To identify prognostic risk factor groups associated with mortality in this patient population.
Main Methods:
- Retrospective analysis of a new-user cohort from U.S. medical oncology databases (ConcertAI, Flatiron, COTA).
- Inclusion of patients with advanced or metastatic EGFRm NSCLC initiating first-line osimertinib monotherapy (April 2018 - October 2022).
- Kaplan-Meier method for rwOS estimation and multivariate analysis for risk factors.
Main Results:
- Median rwOS was 28.6 months in 1323 patients, with a median follow-up of 20 months.
- High-risk subgroups (ECOG ≥ 2, brain/liver metastases, TP53 co-mutation) showed significantly higher risk of death (p ≤ 0.011).
- 95% of patients had at least one high-risk factor; 33% did not receive second-line therapy.
Conclusions:
- Long-term survival for advanced EGFRm NSCLC patients treated with first-line osimertinib remains suboptimal despite treatment advances.
- The high prevalence of risk factors underscores the need for improved therapeutic strategies.
- A significant proportion of patients not receiving second-line therapy indicates potential barriers or disease progression challenges.
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