Recurrent Non-Small Cell Lung Cancer: a Perplexing Problem

Treating non-small cell lung cancer (NSCLC) after it becomes resistant to chemotherapy has been the subject of intense scientific and clinical research. The study of targeted therapy, in which a drug or biological agent attaches only to a specific receptor on a malignant cell, led to the approval and release of the anilinoquinazolines gefitinib (Iressa) and erlotinib (Tarceva), for the treatment of patients with NSCLC who have failed or can no longer tolerate chemotherapy.

While erlotinib has shown a survival benefit in clinical trials, in a recent study called the ISEL trial gefitinib did not show any improvement in survial compared to placebo. This is frustrating to say the least since the two agents go to the same molecular target – the EGFR, or epidermal growth factor receptor! One piece of evidence to explain this is a study showing that certain specific somatic mutations in the EGFR gene correlate with dramatic responses to the agent gefitinib.

Now researchers a Harvard Medical School and the Case School of Medicine in Cleveland have just published a study showing that a patient with EGFR-mutant, gefitinib-responsive NSCLC who relapsed after two years of therapy with gefitinib developed a second point mutation, leading to gefitinib resistance.

The authors conclude that repeat biopsies of tumors may be necessary to monitor patients for the development of resistance when using novel targeted therapies – especially against mutations in the EGFR, since such mutations may require a change in therapy.

My conclusion is: Egad, do we medical oncologists have a lot of reading to do to keep current!