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Targeted therapies in lung cancer and Biomarkers

16 December 2010  •  Author(s): Wolfgang M. Brueckl & Joachim Ficker, Department of Internal Medicine 3, Lung Cancer Center and Thomas M. Mundel, Roche Parma AG

Despite innumerable clinical studies in the past three decades with lots of traditional chemotherapeutical drugs and drug combinations, survival in lung cancer has increased by far less than other entities. Research now focuses on inhibitors of tyrosine kinases which have been shown to have a central role in the development of lung cancer. However, as recent developments show, unselected use of those ‘targeted therapies’ is not always effective and may even be harmful to lung cancer patients if given at the wrong time or to the wrong patient. Biomarkers with predictive value will, in future, be of utmost importance for an individualised tumour tailored therapy. In this perspective, we describe the latest developments in EGF-R directed tyrosine kinase inhibitors and other targeted therapies. Additionally, the actual (limited) predictive role of biomarkers is discussed in this context and further directions are pinpointed.

Lung cancer is the main cause of malignant tumour deaths in the world with more than 1.2 million cancer deaths per year and is divided in to small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). The latter accounts for approximately 80 per cent of lung cancer and will be the subject of this review. Prognosis of patients with lung cancer is worse in contrast to other tumour entities such as colorectal or breast cancer. With respect to tumour stage and therapy, the five-year survival rate differs between 14 per cent (all stages) and 67 per cent (after surgery with curative intent).

At least 40 per cent of the patients are diagnosed with metastatic disease. Beside best supportive care (BSC), a chemotherapy in palliative intent is recommended for patients with good or acceptable performance status. Using anti-tumour drugs, survival of those patients was improved from 2002 to 2009 with median survival times of 7.9 months to 11.3 months1,2. Usually a combination therapy with a cisplatin or carboplatin based back bone is used. Approved combination partners are taxans, cell-spindle inhibitors or antimetabolites. To date, the only approved antibody in combination therapy is bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, leading to an increase of median survival of 12.3 months in clinically and histologically selected cases3. Because of the enormous range in effect, the type and severity of toxicity and the negative impact of quality of life between the substances, an individualised therapeutic approach would be more than desirable. However, to achieve this goal, validated predictive biomarkers must be known for prejudging the effect of the selected substance in each patient before starting the treatment.

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