The PARAMOUNT trial: a phase III randomized study of maintenance pemetrexed versus placebo immediately following induction first-line treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer.

The search for new agents and for innovative strategies is warranted in the treatment of advanced non small cell lung cancer (NSCLC) because the outcomes remain unsatisfactory for most patients. Maintenance treatment with either a chemotherapeutic agent or a molecularly targeted agent after first-line chemotherapy is a very interesting strategy that has been largely investigated in the last years. Maintenance treatment can consist of drugs included in the induction regimen (continuation maintenance) or other non-cross-resistant agents not included in the induction regimen (switch maintenance). The switch maintenance strategy with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor erlotinib (in all the histologies) or with pemetrexed (in non-squamous histologies) have been demonstrated to be two possible effective options versus the classic break from cytotoxic chemotherapy after a fixed course in the treatment of advanced NSCLC. However some biases may have influenced the outcomes of switch maintenance trials as the low rate of patients treated with erlotinib and pemetrexed in the placebo arms. Very recently, a randomized phase III trial named PARAMOUNT has demonstrated a clinically significant benefit in overall survival with a good safety profile versus placebo in favour of continuation maintenance with pemetrexed after four cycles of induction with cisplatin plus pemetrexed. Continuation maintenance can be considered the true maintenance strategy because switch maintenance is an early second-line treatment. Continuation maintenance with pemetrexed after cisplatin plus pemetrexed induction for patients selected for a maintenance strategy is recommended as first-line treatment of advanced non-squamous NSCLC.