Real-world outcomes of treatment strategy between first-line osimertinib, first/second-generation EGFR-TKIs followed by osimertinib and without osimertinib in advanced EGFR-mutant NSCLC

Background

Osimertinib has been the standard of care in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We evaluated outcomes between osimertinib and first/second-generation (1G/2G) EGFR-tyrosine kinase inhibitors (TKIs) as first-line (1L), and investigated how T790M status and sequential osimertinib after 1G/2G EGFR-TKI failure affected overall survival (OS).

Materials and methods

We retrospectively evaluated the outcomes of patients with advanced NSCLC harboring exon 19 deletion or L858R mutation who received osimertinib and 1G/2G EGFR-TKIs as 1L treatment from January 2015 to March 2021. In the exploratory analysis, we analyzed the outcomes among three groups: osimertinib as 1L (1L-Osi), 1L 1G/2G EGFR-TKIs followed by osimertinib (2L-Osi), and 1L 1G/2G EGFR-TKIs without osimertinib (No-Osi). Propensity score matching (PSM) and 12-month landmark analysis were used to mitigate selection bias and immortal time bias.

Results

Of 485 patients, 213 and 272 received 1L osimertinib and 1L 1G/2G EGFR-TKIs. All 2L-Osi patients had T790M mutations after 1G/2G EGFR-TKI failure. OS did not differ according to 1L EGFR-TKIs [osimertinib versus 1G/2G EGFR-TKIs; 33.7 versus 41.8 months; hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.65-1.29]. In the 12-month landmark analysis, the median OS was 34.4 months [95% CI 21.3 months-not reached (NR)] in 1L-Osi, 63.8 months (95% CI 46.0 months-NR) in 2L-Osi, and 22.5 months (95% CI 19.0-35.3 months) in No-Osi. After PSM, similar results were observed.

Conclusions

There was no significant difference in OS between osimertinib and 1G/2G EGFR-TKIs as 1L treatment in patients with EGFR-mutant NSCLC. However, 2L osimertinib following 1L 1G/2G EGFR-TKIs in patients who would acquire T790M mutation has been linked to a better prognosis compared to 1L osimertinib.