Vaccination therapy for non-small-cell lung cancer: review of agents in phase III development

The historical results of cancer vaccination for non-small-cell lung cancer (NSCLC) were disappointing. In the current decade, however, new insights in the interaction between tumours and the immune system have led to the development of immunotherapy as a fundamentally new concept for the treatment of NSCLC. Modern NSCLC vaccine strategies rely on better identification of antigenic targets, addition of strong immunoadjuvants, and use of more efficient delivery systems. These treatments have convincingly demonstrated to elicit potent immune responses and have shown promising efficacy signals and excellent tolerability in phase II randomised studies. This-together with recent positive phase III data in indications other than NSCLC-has helped to establish the proof of principle for cancer vaccination. In NSCLC, ongoing phase III trials are investigating this approach in different treatment settings: the Melanoma AntiGEn A3 vaccine in resected early-stage NSCLC, the L-BLP25 vaccine in locally advanced NSCLC after chemoradiotherapy, and belagenpumatucel-L, the epidermal growth factor and the TG4010 vaccine in advanced stage, either as an adjunct to chemotherapy or as maintenance after completion of chemotherapy. Mode of action, development, available clinical data, and currently ongoing phase III studies are reviewed.