More people in the United States die from lung cancer than any other type of cancer. A recent report from the American Cancer Society estimates that there will be a total of 226,160 newly diagnosed cases of lung cancer in the US in 2012; of these, 160,340 will die of the disease.1 With this staggering mortality rate, there is an ever-increasing need for effective therapeutics with low toxicity in order to prolong life and improve quality of life for these patients.
Platinum-based chemotherapies, including paclitaxel and carboplatin, are currently the standard of care for the treatment of lung cancer. Despite the notorious toxicity profiles of these agents, they remain the recommended first-line therapy for the treatment of this dreaded disease. It is no surprise that there is so much toxicity associated with platinum-based drugs because they have inadequate cell specificity.
The need for highly targeted lung cancer therapies is clear, and that unmet medical need might be satisfied by the use of biologics. Anticancer therapeutics target tumors by two interrelated approaches: gene-mutation-based targeting and receptor-based targeting. An example of the gene mutation-based targeting approach is the use of the anticancer drug crizotinib (XALKORI®, Pfizer) to treat patients with non-small cell lung cancer (NSCLC), which harbor mutations in the EML4-ALK fusion translocation oncogene.2 An example of a receptor-based targeting agent is cetuximab (Erbitux®, Eli Lilly and Company), which inhibits the growth of tumors that harbor mutated forms of epidermal growth factor receptor (EGFR). Using cetuximab, a monoclonal antibody, to target mutated forms of EGFR and disrupt their function can halt cancer progression in many tumor types, including lung cancer.
Targeted therapies, including biologics, are expensive, and not all patients respond to them. For these reasons, it is crucial to identify biomarkers predictive of response and potential drug resistance. Several clinical trials have shown the benefits and disappointments of biologics in the treatment of lung cancer. However, no one trial has demonstrated a consistent benefit of biologics, thus continuing the challenges facing the acceptance of this form of targeted therapy as first-line treatment for this deadly disease.
Bevacizumab (Avastin®, Genentech)
One clinical trial examined whether adding bevacizumab to the standard of care with carboplatin and paclitaxel would improve survival in elderly patients with NSCLC.3 Data from 4,168 patients aged 65 years or older with stage IIIB or stage IV NSCLC diagnosed between 2002 and 2007 were categorized into three cohorts based on diagnosis year and type of initial chemotherapy administered within 4 months of diagnosis.