Advanced Lung Cancer Patients' Use of EGFR Tyrosine Kinase Inhibitors and Overall Survival: Real-World Evidence from Quebec, Canada

Abstract

EGFR tyrosine kinase inhibitors (EGFR-TKIs) are breakthrough palliative treatments for advanced lung cancer patients with tumors harboring mutations in the EGFR gene. Using healthcare administrative data, three cohorts were created to describe the use of three EGFR-TKIs that are publicly funded in Quebec for specific indications (i.e., 1st-line gefitinib, 1st-line afatinib, and post-EGFR-TKI osimertinib). The main objective was to compare overall survival (OS) among patients receiving these treatments to those in previous experimental and real-world studies. The patients who received EGFR-TKIs for indications of interest between 1 April 2001, and 31 March 2019 (or 31 March 2020, for post-EGFR-TKI osimertinib) were included to estimate the Kaplan-Meier-based median OS for each cohort. An extensive literature search was conducted to include comparable studies. For the gefitinib 1st-line (n = 457), the afatinib 1st-line (n = 80), and the post-EGFR-TKI osimertinib (n = 119) cohorts, we found a median OS (in months) of 18.9 (95%CI: 16.3-21.9), 26.6 (95%CI: 13.7-NE) and 19.9 (95%CI: 17.4-NE), respectively. Out of the 20 studies that we retained from the literature review and where comparisons were feasible, 17 (85%) had similar OS results, which further confirms the value of these breakthrough therapies in real-world clinical practice.

Keywords: advanced cancer; epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs); metastatic cancer; non-small cell lung cancer (NSCLC); real-word evidence; real-world data; survival; targeted therapies; treatment utilization.

Figure A1

Classification of patients according to the line of treatment with 1st EGFR-TKI.

Figure A2

Flow Diagram of the Article Selection Process. ^a 1 article [28] included 2 randomized controlled trials (i.e., 2 studies) on afatinib as 1st-line treatment. ^b 1 article [34], which included 1 real-world study, was counted twice since it was used in the indirect comparisons of EGFR-TKIs for 2 indications: 1st-line gefitinib treatment and 1st-line afatinib treatment.

Figure 1

Flowchart of study populations in EGFR-TKI cohorts: (a) 1st-line gefitinib cohort; (b) 1st-line afatinib cohort; (c) Post-EGFR-TKI osimertinib cohort. Abbreviations: Pts: Patients. ¹ End of follow-up: 31 March 2020. ² Gefitinib, afatinib, or erlotinib.

Figure 2

Distribution of New Users of Each EGFR-TKI for Specific Indications, by Fiscal Year.

Figure 3

Distribution of total days’ supply: (a) 1st-line gefitinib cohort (N = 457); (b) 1st-line afatinib cohort (N = 80); (c) Post-EGFR-TKI osimertinib cohort (N = 119). Abbreviations: min: minimum; Q1: quartile 1; Q2: quartile 2 or median; Q3: quartile 3; max: maximum. The lower limit of the boxplot mustache represents the minimum, whereas the superior limit is equal to 1.5 times the interquartile range (Q3 minus Q1) plus Q3.

Figure 4

Overall survival: (a) 1st-line gefitinib cohort (N = 457); (b) 1st-line afatinib cohort (N = 80); (c) Post-EGFR-TKI osimertinib cohort (N = 119). Abbreviations: 95% CI: 95% confidence interval. The grey area around the curves represents the 95% confidence intervals.

Figure 5

Comparison of overall survival estimates with RCTs and real-world studies: (a) 1st-line gefitinib; (b) 1st-line afatinib; (c) Post-EGFR-TKI osimertinib cohort. * Studies submitted to INESSS for evaluation. Abbreviations: RCT: randomized controlled trial; NE: upper bound of 95% confidence interval is non-evaluable. The mustache around each estimate represents the 95% confidence interval. The orange or green square with a blue outline represents a median that is considered similar to Quebec’s median.