Maintenance therapies in advanced non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) has the second highest incidence of any newly diagnosed cancer and also has the highest mortality of any cancer type [1]. The majority of patients present with late-stage disease, by which time systemic therapy (chemotherapy) has become the primary treatment and platinum doublet chemotherapy is the first-line choice among patients with advanced disease (stage IIIB/IV). These treatments have produced modest but clinically significant gains in overall survival (OS) [2]. Attempts to improve on these survival benefits, utilizing longer treatment durations or continuation of chemotherapy with a different agent, such as docetaxel or gemcitabine, beyond four to six cycles or until disease progression, have resulted in no significant gains [3–5]. In fact, continuation of these therapies has only provided improvements in progression-free survival (PFS), with increased toxicity and no improvement in OS. Until recently, the American Society of Clinical Oncology (ASCO) guidelines recommended that all patients with good performance status (PS) discontinue first-line cytotoxic chemotherapy at disease progression, after four cycles in nonresponders and, regardless of ongoing response, patients discontinue cytotoxic therapy after a total of six cycles [6]. To date, with the accummulation of more data, patients can be considered for maintenance therapy, which is initiated following a platinumbased treatment in the setting of no evidence of progression [7–11]. There are two types of maintenance therapy, both adapted from the National Comprehensive Cancer Network [101]: continuation maintenance, which refers to the ongoing administration of at least one of the agents used in the first-line, and switch maintenance, which refers to the initiation of a different agent not included in the first-line regimen, continued in the absence of progression after four to six cycles of initial therapy [12]. The major goals of maintenance therapy are to improve the survival benefit of first-line therapy without significant increases in toxicity or decreases in quality of life (QOL). This article will focus on the most recent data presented on continuation and switch main tenance therapy, with a focus on both cytotoxic and biological agents, including docetaxel, gemcitabine, pemetrexed, erlotinib, bevacizumab and cetuximab.