Three-arm randomised controlled phase 2 study comparing pemetrexed and erlotinib to either pemetrexed or erlotinib alone as second-line treatment for never-smokers with non-squamous non-small cell lung cancer

Use of the Epidermal Growth Factor Receptor Inhibitors Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Icotinib in the Treatment of Non-Small-Cell Lung Cancer: A Systematic Review

“…The overall response rate was significantly higher for gefitinib (30.1% vs. 14.9%, p < 0.001) 96 . Progression-free survival was significantly longer for patients randomized to gefitinib (9.4 months vs. 2.9 months, p = 0.010) and also for patients randomized to a combination of erlotinib and pemetrexed (7.4 months vs. 3.8 months for erlotinib and 4.4 months for pemetrexed alone; hr: 0.57; 95% ci: 0.40 to 0.81; p = 0.002) 97 . However, the survival rates were nonsignificantly different (p = 0.89) 96,97 .…”

Dose erlotinib add beneficial effect on cytotoxic agent for patients with pretreated advanced non-small cell lung cancer?

“…The study by Lee et al demonstrated that PFS, the primary endpoint, was improved by combination of erlotinib with pemetrexed in never-smokers with advanced NSCLC, but no statistically significant difference was found in OS, the secondary endpoint, between pemetrexed plus erlotinib and either single agent. The benefit was observed across multiple clinical and biomarker subgroups [29] . In the single arm study by Sangha on combination of intermittent erlotinib with tri-weekly docetaxel, the RR (28.1%) met the expected value (20%).…”

“…There are four phase II studies of combination of erlotinib with a cytotoxic agent; three pemetrexed studies [28][29][30][31] and one docetaxel study [24] ( Table 2).…”

Gefitinib with pemetrexed as first-line therapy in patients with advanced nonsquamous non-small cell lung cancer with activating epidermal growth factor receptor mutations

“…Mean PFS was 16.8 months (11). In the second-line setting, pemetrexed (day 1) plus intercalated erlotinib (day 2-14 of a 21-day cycle) could improve its PFS in non-smoking and nonsquamous cell carcinoma patients compared with either erlotinib or pemetrexed alone (12). In the randomized phase II trial of erlotinib alone or with carboplatin and paclitaxel (up to six cycles), the addition of chemotherapy could not prolong PFS (5.0 vs. 6.6 months, P=0.1988) in patients who were never or light former smoker with advanced lung adenocarcinoma (CALGB 30406 trial) (13).…”

“…So the enhancement of cytotoxicity when pemetrexed is added to gefitinib might suppress the small subpopulation of cells harboring T790M mutation or with the mesenchymal phenotype. Preclinical studies indicated there is cell cycle dependent synergism or antagonism when combining chemotherapy and EGFR TKI, however clinical data do not support it well (10)(11)(12)(13)(14)(15)(16).…”