The role of pemetrexed as maintenance treatment in advanced NSCLC: a Phase III randomized trial.

A randomized Phase III trial tested the efficacy of pemetrexed as maintenance treatment in patients with advanced non-small-cell lung cancer (NSCLC) who were without progression after completing four cycles of first-line platinum-based chemotherapy. The primary endpoint of the trial was progression-free survival (PFS). Pemetrexed was significantly better than placebo both in terms of PFS and overall survival. The study was not designed as a direct comparison between 'early' and 'delayed' administration of pemetrexed because there was no mandatory cross-over in the control arm, in which less than 20% of patients actually received pemetrexed as second-line. However, a relevant proportion of patients with advanced NSCLC, due to early death or clinical deterioration, will never be able to receive a second-line treatment after disease progression. At the end of first-line treatment, the immediate administration of a drug that has not been received before (instead of adopting the 'wait and watch' approach based on stopping treatment until disease progression) could be a positive strategy, allowing patients to receive early one more potentially active drug without an unacceptable increase in toxicity. This strategy should be discussed with patients. Prespecified analysis of efficacy by tumor histology showed a significant interaction between treatment and histology, with pemetrexed producing significant and clinically meaningful benefit compared to placebo in the non-squamous group, without efficacy in patients with squamous tumors.