Accelerated second-line or maintenance chemotherapy versus treatment at disease progression in NSCLC

For many decades, the use of chemotherapy as second-line therapy in non-small-cell lung cancer relied upon disease progression. Several studies have shown that four to six cycles of chemotherapy administered as front-line therapy treatment offers a survival advantage to patients; however, further chemotherapy beyond this initial treatment was more associated with side effects and no benefit in survival. Until 2009, second-line treatment for lung cancer was well established for three therapeutic agents: docetaxel, pemetrexed and erlotinib. Currently, the timeframe to use these agents has been challenged by two large randomized clinical trials in which pemetrexed (JMEN trial) and erlotinib (Sequential Tarceva in Unresectable NSCLC [SATURN] trial) were used as 'maintenance' therapy and shown to impact progression-free survival and overall survival. This review focuses on the actual dilemma that medical oncologists face in clinical practice in terms of when and to whom maintenance therapy should be applied or if the 'watch and wait' approach prior to start second-line therapy is still advisable.