Background: The optimal treatment sequence of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) and pemetrexed in previously treated advanced lung adenocarcinoma patients is currently unknown.
Methods: This retrospective study explored two sequential regimens incorporating EGFR TKIs and pemetrexed in advanced lung adenocarcinoma patients who had failed standard first-line chemotherapy. The medical records of 83 patients were carefully reviewed. 45 patients who received second-line EGFR TKIs followed by third-line pemetrexed were grouped as cohort A. 38 patients who received a strategy with the reverse sequence were grouped as cohort B. Progression-free survival, disease control duration and survival time were compared between the two cohorts.
Results: Median survival time is significantly longer in cohort A compared with cohort B (23.615 months vs. 16.269 months, HR: 0.549, 95% CI: 0.308-0.979, P = 0.042). Median disease control duration is 17.463 months in cohort A versus 11.587 months in cohort B (HR: 0.700, 95% CI: 0.409-1.196, P = 0.191). Median progression-free survival with second-line EGFR TKIs is significantly longer than second-line pemetrexed (8.056 months vs. 4.200 months, HR: 0.462, 95% CI: 0.281-0.758, P = 0.001). Median progression-free survival with third-line EGFR TKIs is 6.885 months versus 7.624 months with third-line pemetrexed (HR: 0.462, 95% CI: 0.605-1.767, P = 0.902). The rate of response to EGFR TKIs is higher in second-line setting than in third-line (44% vs. 34%).
Conclusions: We hypothesized that for EGFR-mutated patients, second-line EGFR TKIs followed by third-line pemetrexed is preferable to the reverse sequence.