|Scans show how therapy with CO-1686 has diminished tumors in lungs of patient with T790M mutation, as well as reduced tumors in metastases that have spread to the brain. Graphic: Courtesy of Dr. Jonathan Goldman|
UCLA scientists report that two new experimental drugs have shown great promise in the treatment of patients with non-small-cell lung cancer, which accounts for about 85 percent of all lung cancers. The drugs — ramucirumab and CO-1686 — were shown in separate clinical trials to increase survival times with fewer toxic side effects than standard treatments. The findings of both trials were presented at the annual meeting of the American Society of Clinical Oncology.
Edward Garon, MD (FEL ’06), assistant professor of hematologyoncology, conducted an extensive multi-year Phase 3 clinical trial testing ramucirumab in a population of 1,253 patients whose cancers had progressed during or after first-line chemotherapy treatment. Ramucirumab is an antibody that targets VEGFR-2, an extracellular protein that is important in the formation of the blood vessels that support cancer cells. Patients were given ramucirumab in combination with docetexal, a clinically approved chemotherapy drug considered the cornerstone of second-line treatment in advanced non-small-cell lung cancer. Tumors shrank significantly in 23 percent of patients receiving ramucirumab. The drug is the first new therapy for previously treated nonsmall- cell lung cancer patients to improve overall survival, when added to standard therapy with findings showing a disease-progression-free survival rate of 4.5 months and median overall survival of 10.5 months.
Another class of targeted drugs being investigated is EGFR (epidermal growth factor receptor) tyrosine kinase inhibitors. Recent studies, however, have shown that when a patient develops resistance to EGFR inhibitors, more than half the time it is due to the emergence of a new “gatekeeper” mutation, called T790M. CO-1686 is an investigational drug that has been discovered to selectively target both the initial EGFR mutations and the T790M-resistance mutation.
Jonathan Goldman, MD (FEL ’08), assistant professor of hematology-oncology, was among the leaders of a study of 88 patients with advanced non-small-cell lung cancer who had previously been treated with an EGFR inhibitor and had developed resistance. In a Phase 1 trial, CO-1686 was administered continuously to the patients in 21-day cycles. Response to the drug was seen in 58 percent of the patients. Treatment-related side effects were for the most part mild and manageable.
Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomized phase 3 trial,” The Lancet, June 2014