Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer

Abstract

Abstract. Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular-targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib. IntroductionThe 'elderly' patient with lung cancer treated with cytotoxic chemotherapy has been the subject of several studies that have assumed international importance due to sample size, methodological rigor and impact on clinical practice. Confirmed by evidence-based medicine, these important trials have led to the definition of therapeutic standards validated in this patient subset: The ELVIS study showed the superiority of vinorelbine over placebo (1); the MILES study showed a similar effectiveness between single-agent vinorelbine or gemcitabine, and single-agent efficacy over the combination of vinorelbine plus gemcitabine (2); the MILES 2P study showed better survival for cisplatin plus gemcitabine compared with cisplatin plus vinorelbine (3); the IFCT-0501 study showed survival benefits with carboplatin plus weekly paclitaxel compared with vinorelbine or gemcitabine monotherapy (4); another study showed improved survival with platinum-based adjuvant chemotherapy (5); and in a phase II trial involving elderly patients with advanced-stage small cell lung cancer, the weekly regimen of gemcitabine and docetaxel demonstrated no advantage over standard therapy (6).The last decade of research in this field has witnessed the emergence of molecular-targeted therapies as an essential element for the treatment of patients with non-small cell lung cancer (NSCLC) (7). The studies on the activity of these novel therapies in the elderly patient with NSCLC are few (8,9), comprising a more fragmented and less numerous casuistry tha...

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