EGFR-TKIs combined with chemotherapy versus EGFR-TKIs single agent as first-line treatment for molecularly selected patients with non-small cell lung cancer

EGFR-TKIs added to chemotherapy and EGFR-TKIs single agent have been used as first-line treatment for advanced non-small cell lung cancer patients with and without EGFR mutations. However, direct head-to-head comparison between them is still lacking. We performed indirect comparisons to assess the treatment effects of EGFR-TKIs added to chemotherapy versus EGFR-TKIs alone via common comparator of standard chemotherapy in both subgroups. A comprehensive literature search was undertaken. Finally, 12 randomized controlled trials enrolling more than 2,160 patients with EGFR mutation analysis met the inclusion criteria. We found that EGFR-TKIs combined with chemotherapy did confer an additive PFS advantage over standard chemotherapy both for patients with mutant EGFR tumors (HR 0.54, 95 % CI [0.30, 0.95], P = 0.03) and for patients with wild-type EGFR tumors (HR 0.82, [0.68, 0.98], P = 0.03), but no survival difference between the treatments in both subgroups. When using standard chemotherapy as common comparator, indirect comparison indicated that addition of chemotherapy to EGFR-TKIs did confer an additive PFS benefit (HR 0.38, [0.32, 0.46], P < 0.001) and survival benefit (HR 0.75, [0.66, 0.85], P < 0.001) over EGFR-TKIs alone in patients with wild-type EGFR, but showed a PFS disadvantage (HR 1.35, [1.03, 1.77], P = 0.03) and a marginal trend toward survival disadvantage (HR 1.16, [0.99, 1.35], P = 0.06) compared with EGFR-TKIs alone in patients with mutant EGFR tumors. In summary, addition of chemotherapy to EGFR-TKIs as first-line treatment did confer an additive benefit over EGFR-TKIs alone in patients with wild-type EGFR tumors, but was inferior to EGFR-TKIs alone in patients with mutant EGFR tumors.