Efficacy of pemetrexed as second-line therapy in advanced NSCLC after either treatment-free interval or maintenance therapy with gemcitabine or erlotinib in IFCT-GFPC 05-02 phase III study.

Maintenance therapy in advanced non-small-cell lung cancer (NSCLC) might lead to resistance to subsequent treatments. IFCT-GFPC 0502 study showed a progression-free survival (PFS) benefit with gemcitabine or erlotinib maintenance compared with observation after cisplatin-gemcitabine chemotherapy. The trial included a pre-defined pemetrexed second-line therapy, allowing post-hoc assessment of its efficacy according to previous maintenance treatment or treatment-free interval.Stage IIIB/IV NSCLC patients were randomized after four cycles of cisplatin-gemcitabine chemotherapy to either observation or to receive maintenance therapy with gemcitabine or erlotinib. Pemetrexed was given as second-line treatment on disease progression in all arms. PFS and overall survival (OS) were assessed from the beginning of pemetrexed therapy according to randomization arm.Of the 464 randomized patients, 360 (78 %) received second-line pemetrexed (130 [84%], 114 [74%], and 116 [75%] in observation, gemcitabine, and erlotinib arm, respectively). Median number of pemetrexed cycles was 3 (1-40) in all arms. Median PFS did not differ between gemcitabine and observation arms (4.2 versus 3.9 months, hazard ratio [HR] [95% confidence interval [CI] 0.81 [0.62-1.06]) or between erlotinib and observation arms (4.2 versus 3.9 months, HR 0.83 [0.64-1.09]). OS data showed a non-significant improvement with gemcitabine arm versus observation arm (8.3 versus 7.5 months, HR 0.81 [0.61-1.07]) or erlotinib arm versus observation arm (9.1 versus 7.5 months, HR 0.80 [0.61-1.05]). Results were similar for non-squamous patients. Grade 3 to 4 treatment-related adverse events (AEs) were comparable in all arms.Maintenance therapy with gemcitabine continuation or erlotinib does not seem to impair efficacy of second-line pemetrexed comparatively to administration after a treatment-free interval.