Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor coupled with cytotoxic chemotherapy is extremely effective to treat advanced non-small-cell cancer of the lung (NSCLC) with EGFR mutations however, little is famous concerning the effectiveness and safety of the combination in contrast to those of standard therapy with EGFR- tyrosine kinase inhibitors alone.

Methods: We at random assigned 345 patients with recently diagnosed metastatic NSCLC with EGFR mutations to gefitinib coupled with carboplatin plus pemetrexed or gefitinib alone. Progression-free survival (PFS), PFS2, and overall survival (OS) were sequentially examined as primary finish points based on a hierarchical consecutive testing method. Secondary finish points were objective response rate (ORR), safety, and excellence of existence.

Results: The mixture group shown a much better ORR and PFS compared to gefitinib group (ORR, 84% v 67% [P < .001] PFS, 20.9 v 11.9 months hazard ratio for death or disease progression, 0.490 [P < .001]), although PFS2 was not significantly different (20.9 v 18.0 months P = .092). Median OS in the combination group was also significantly longer than in the gefitinib group (50.9 v 38.8 months hazard ratio for death, 0.722 P = .021). The rate of grade ≥ 3 treatment-related adverse events, such as hematologic toxicities, in the combination group was higher than in the gefitinib group (65.3% v 31.0%) there were no differences in quality of life. One treatment-related death was observed in the combination group.

Conclusion: Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.