Abstract

The discovery of EGFR tyrosine kinase inhibitors (TKI) for the treatment of EGFR mutant (EGFRm) metastatic NSCLC is regarded as a landmark in lung cancer. EGFR-TKIs have now become a standard first-line treatment for EGFRm NSCLC. The aim of this retrospective cohort study is to describe real-world patterns of treatment and treatment outcomes in patients with EGFRm metastatic NSCLC who received EGFR-TKI therapy outside of clinical trials. One hundred and seventy EGFRm metastatic NSCLC patients were diagnosed and initiated on first-line TKI therapy between 2004 and 2018 at the Peter Brojde Lung Cancer Centre in Montreal. Following progression of the disease, 137 (80%) patients discontinued first-line treatment. Moreover, 80/137 (58%) patients received second-line treatment, which included: EGFR-TKIs, platinum-based, or single-agent chemotherapy. At the time of progression on first-line treatment, 73 patients were tested for the T790M mutation. Moreover, 30/73 (41%) patients were found to be positive for the T790M mutation; 62/80 patients progressed to second-line treatment and 20/62 were started on third-line treatment. The median duration of treatment was 11.5 (95% CI; 9.62–13.44) months for first-line treatment, and 4.4 (95% CI: 1.47–7.39) months for second-line treatment. Median OS from the time of diagnosis of metastatic disease was 23.5 months (95% CI: 16.9–30.1) and median OS from the initiation of EGFR-TKI was 20.6 months (95% CI: 13.5–27.6). We identified that ECOG PS ≤ 2, presence of exon 19 deletion mutation, and absence of brain metastases were associated with better OS. A significant OS benefit was observed in patients treated with osimertinib in second-line treatment compared to those who never received osimertinib. Overall, our retrospective observational study suggests that treatment outcomes in EGFRm NSCLC in real-world practice, such as OS and PFS, reflect the result of RCTs. However, given the few observational studies on real-world treatment patterns of EGFR-mutant NSCLC, this study is important for understanding the potential impact of EGFR-TKIs on survival outside of clinical trials. Further real-world studies are needed to characterize patient outcomes for emerging therapies, including first-line osimertinib use and combination of osimertinib with chemotherapy and potential future combination of osimertinib and novel anticancer drug, outside of a clinical trial setting.

Highlights

  • Lung cancer is the most common cancer worldwide, accounting for 2.1 million new cases and 1.8 million deaths in 2018 [1]

  • This review was performed to determine whether—in patients with epidermal growth factor receptor (EGFR) mutant (EGFRm) metastatic non-small cell lung cancer (NSCLC)—real-world outcomes achieved with tyrosine kinase inhibitors (TKI) therapy are comparable to randomized clinical trials (RCT) outcomes reported in RCTs

  • The second-line treatment patterns we identified are similar to those recommended in the guidelines [18,19]: 54% of these patients were started on another TKI and 34% started on systemic chemotherapy

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Summary

Introduction

Lung cancer is the most common cancer worldwide, accounting for 2.1 million new cases and 1.8 million deaths in 2018 [1]. In Canada, in 2020, an estimated 21,200 people died from lung cancer. This represents 25% of all cancer deaths [2]. The treatment of lung cancer is the fastest developing area and the guidelines are continuously evolving, compared to other cancers [3]. A major advancement in the treatment of non-small cell lung cancer (NSCLC) has been the discovery of genomic abnormalities (or oncogenic drivers) that drive the development of certain types of lung cancer [4,5,6]. In Western countries, EGFR mutations are present in 10–35% of NSCLC cases, but the prevalence of these mutations is not uniform among populations; it tends to be more prevalent in females, non-smokers, and patients with bronchioloalveolar features in tumor specimens [8,9,10]

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