Maintenance Therapy for Advanced-Non Small Cell Lung Cancer

ABSTRACT

Until recently standard first-line treatment for advanced non-small cell lung cancer (NSCLC) consisted of up to 4-6 cycles of platinum-based chemotherapy which contrasted practices in the management of other solid tumors. Curtailing the duration of chemotherapy was a reflection of the rather poor efficacy of regimens for NSCLC and their poor tolerability that did not facilitate long-term use. With the development of new active agents, the concept of prolonging the duration of initial therapy in the absence of disease progression as maintenance or “continuation maintenance” (i.e. same regimen or part of the regimen) or consolidation or “switch maintenance” (i.e. switch to a different agent) has now emerged and is the topic of some controversy. Recent well designed phase III clinical trials showed improvement in overall survival (OS) and/or progression-free survival (PFS) in this setting with agents like docetaxel (PFS, not OS), pemetrexed (OS and PFS), and erlotinib (OS and PFS in one study, PFS only in another). Moreover, bevacizumab and cetuximab were continued until progression after given concurrently with platinum doublets in the two pivotal trials that demonstrated survival benefits with these agents in advanced NSCLC. A major criticism of some maintenance trials has been the lack of cross-over to the study drug in the control arm at the time of progression (i.e. as second-line therapy). In the pemetrexed and erlotinib studies, only about 20% of patients randomized in the placebo arm received the study drug at progression. In the docetaxel study that was the only one that had pre-specified treatment with the same drug at the time of progression, 63% of patients received delayed docetaxel which may have influenced the overall survival difference between the 2 arms. Any survival benefit from maintenance therapy will have to be balanced against expected toxicities, impact on quality of life and associated costs. In conclusion, maintenance therapy has become an option in the treatment of advanced NSCLC. However, treatment decisions should always be individualized and based on patient’s performance status and co-morbidities, tumor response, histology, presence of EGFR mutations and possibly other emerging biomarkers.

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