Efficacy of platinum-based combination chemotherapy in advanced lung adenocarcinoma harboring sensitive epidermal growth factor receptor (EGFR) mutations with acquired resistance to first-line EGFR tyrosine kinase inhibitor (TKI)

Background The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) eventually fails in treating advanced lung adenocarcinoma harboring sensitive EGFR mutations because of acquired resistance. In clinical practical setting, platinum-doublet chemotherapy has been frequently performed after failure of first-line EGFR-TKIs. The efficacy of different regimens was compared. Methods From January 2012 to December 2013, 160 patients with mutated EGFR receiving first-line EGFR-TKIs and second-line chemotherapy were analyzed retrospectively. Sixty-eight patients received pemetrexed-based therapy and among them, 61 were in combination with cisplatin. Ninety-two patients received non-pemetrexed-based therapy and among them, 79 were combined with cisplatin. Results The progression-free survival of first-line EGFR-KI was 9.0 and 8.6 months for pemetrexed and non-pemetrexed treatment groups respectively (HR: 0.9146, 95% CI: 0.6656 to 1.257, P=0.5818). The median progression-free survival (PFS) of second-line therapy was 8.3 and 5.6 months for pemetrexed and non-pemetrexed treatment groups respectively (HR: 0.4217, 95% CI: 0.2952 to 0.6025, P=0.0001). The median overall survival (OS) after first-line EGFR-TKIs was 16.9 and 10.3 months for pemetrexed and non-pemetrexed groups respectively (HR: 0.5160, 95% CI: 0.3381 to 0.7873, P=0.0021). For those receiving pemetrexed continuous maintenance therapy, there was 18.7 months of survival after first-line EGFR-TKI, compared to 11.1 months for those without maintenance (HR: 0.4012, 95% CI: 0.2577 to 0.6247, P <0.0001). Conclusion The efficacy of pemetrexed was superior to other chemotherapeutic agents in second line treatment for patients with lung adenocarcinoma harboring sensitive EGFR mutations after first-line EGFR-TKI therapy. Continuous maintenance pemetrexed therapy also improved the PFS and OS.