Although lung cancer is still a deadly disease—responsible for more than 150,000 deaths each year in the United States alone—there is some remarkably good news when it comes to lung cancer treatment. As researchers learn more about how the disease grows, they are finding promising therapies for even the most challenging lung cancers to treat.
Targeted therapies have been an important advance in the treatment of patients with non–small cell lung cancer, the most common type of lung cancer. These drugs target specific mutations found in patients with NSCLC—namely, in the epidermal growth factor receptor (EGFR) gene and in the ALK gene. The targeted drugs block, or inhibit, the effects of these mutations and cause tumors to shrink as a result. They can be effective at first, but patients eventually become resistant to them, meaning they no longer cause the tumors to shrink. As a result, patients with NSCLC need effective new treatment options.
Fortunately, scientists increasingly understand why patients become resistant to targeted therapies and how they can develop drugs that overcome this resistance. As a result, in recent years they have made promising discoveries in treatment for NSCLC that is resistant to both EGFR and ALK inhibitors.
Scientists have made important steps in overcoming resistance to EGFR inhibitors by discovering another mutation that they believe causes a cancer’s resistance to EGFR-targeted therapy: the T790M mutation. They have been testing two experimental drugs— AZD929118 and CO-1686— designed to target T790M. Results so far are promising: in early studies approximately 50 percent of T790M-positive patients who received AZD9291 and close to 60 percent of those who received CO-1686 experienced tumor shrinkage. A significant next step in research will be to see if these drugs improve long-term survival for patients with NSCLC that is resistant to EGFR inhibitors.1
Researchers have also found encouraging activity in the treatment of NSCLC that is resistant to ALK inhibitors. The investigational compound Zykadia appears highly active in patients with advanced ALK-positive NSCLC.2
Zykadia is an ALK inhibitor but so far appears more effective than one of the standard treatments for advanced ALK-positive NSCLC, Xalkori. In early trials Zykadia has shown greater anti-tumor activity than Xalkori. In one trial, where patients (most of whom had ALK-positive NSCLC) received the maximum tolerated dose of Zykadia (as determined in an earlier study), the majority of participants experienced a clinical response to Zykadia. The overall response rate among patients with ALK-positive NSCLC was 58 percent, and the median progression-free survival was seven months.
(http://news.cancerconnect.com/encouraging-news-for-patients-with-treatment-resistant-lung-cancer/#_ednref1 "1") Sequist LV, Soria JC, Gadgeel SM, et al. First-in-human evaluation of CO-1686, an irreversible, highly selective tyrosine kinase inhibitor of mutations of EGFR (activating and T790M). Journal of Clinical Oncology. 2014;32:5s (suppl.). Abstract 8010.
(http://news.cancerconnect.com/encouraging-news-for-patients-with-treatment-resistant-lung-cancer/#_ednref2 "2")Shaw AT, Kim DW, Mehra R, et al: Ceritinib in ALK-rearranged non-small-cell lung cancer. New England Journal of Medicine. 2014;370(13):1189-1197. doi: 10.1056/NEJMoa1311107.
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