P3.02b-081 Comparative Outcome Assessment of EGFR TKIs for the Treatment of Advanced Non-Small-Cell Lung Cancer: A Network Meta-Analysis: Topic: EGFR Clinical

Abstract

Patients with advanced non-small-cell lung cancer (NSCLC) whose tumors harbor activating mutations in the epidermal growth factor receptor (EGFR) gene, derive substantial clinical benefit from treatment with first and second-line EGFR tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib, erlotinib and afatinib. However, their comparative effectiveness in this setting has not been evaluated, due to the paucity of randomized comparative clinical trials. We performed a comprehensive literature search in PUBMED, EMBASE, SCOPUS and ISI databases for randomized clinical trials evaluating either of the aforementioned EGFR-TKIs in first- and subsequent-lines treatment of EGFR-positive advanced NSCLC. All sensitizing mutations to EGFR-TKI inhibition were included in the current analysis. Patients with active brain metastases, with ECOG performance status of more than 2, as well as trials comparing the combination of EGFR-TKI with chemotherapy to chemotherapy alone were excluded. Comparative study outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and rate of adverse events (AE). Cochrane guidelines were used for statistical analysis. 13 randomized trials incorporating 3,853 patients were eligible for the analysis. In the first-line setting, all EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR rates for gefitinib, erlotinib and afatinib in first-line were 71.5%, 70.2% and 50.1% respectively. HRs for PFS were 0.40 (95% CI: 0.31- 0.50) for gefitinib, 0.25 (0.11-0.56) for erlotinib and 0.40 (0.28-0.57) for afatinib, all three with p<0.001. Respective HRs for OS were 0.89 (0.72-1.10) for Gefitinib, 0.91 (0.76-1.13) for erlotinib and 1.05 (0.88-1.25) for afatinib. No significant differences were detected regarding common AEs (rash, diarrhea) among the three agents. Evidence data for gefitinib were less heterogeneous than those for erlotinib and afatinib. When compared indirectly, gefitinib exhibited the more consistent results from a statistical point of view and erlotinib had the more favorable profile regarding PFS prolongation. These data challenge the current landscape of first and second generation EGFR-TKIs in EGFR mutant advanced NSCLC and especially those of the recently reported LUX-LUNG 7 trial.