Molecular testing

Because of the historically poor outcomes of lung cancer patients, suboptimal therapeutic efficacy, and significant side effects of chemotherapy, and the need to choose more efficacious treatment regimens, and patients most likely to benefit from them, there is a need to predict a priori whether an individual patient’s tumor will respond to a particular therapeutic agent. However, virtually all lung cancer tumor samples available today are from resection specimens so direct, intra-patient molecular-clinical therapy correlations are impossible. In other words, a given resected patient may have been cured without the intervention or because of it – it is impossible to tell. In addition, since the major target of systemic therapy, including adjuvant therapy, is the metastatic lesion, the lack of biospecimens from patients with advanced disease is a major hurdle to advancing the state of the art in applying individual tumor characteristics to the real-world management of patients.

Patients with more advanced disease, those who are determined to be medically inoperable, and patients whose cancer recurs after surgery as well as patients with SCLC, are treated with chemotherapeutic agents, radiotherapy, or a chemotherapy and radiotherapy combination. Only a minority of tumors show objective clinical responses to chemotherapy: the best platinum-based regimens can induce a clinical response in about 30 to 40% of tumors, while gefitinib or erlotinib, low-toxicity tyrosine kinase inhibitors induce an objective response in about 10% of cases.

Specific molecular features of tumors, particularly EGFR mutations and EML4-ALK fusions, have been shown in multiple studies to have prognostic importance and/or be associated with benefit from specific interventions. Other candidate biomarkers are under study that could be of great clinical significance. In spite of this knowledge, only a tiny minority of patients with lung cancer, especially advanced stage lung cancer, are having these molecular assessments performed.

In response to this widely-acknowledged and systematic barrier to progress against lung cancer, the Addario Lung Cancer Medical Institute (ALCMI) has developed and launched targeted, multi-institutional tissue and data repositories. ALCMI is already helping to revolutionize the current standard of care for lung cancer patients through its inaugural collaborative research project termed CASTLE. The purpose of this clinical trial is to facilitate application of the known biomarkers to patients presenting today, and to establish such a collection of biospecimens that will be useful for discovering and validating new biomarkers for future use.

“Prior to the formation of ALCMI, less than 20% of diagnosed lung cancer patients were benefiting from molecular testing. Hopefully this is the beginning of personalized medicine for lung cancer patients.”

– Robert O. Dillman, M.D.,F.A.C.P. Executive Medical and Scientific Director, Hoag Cancer Institute