Clinical Trial Points to Promising Drug Combo for Lung Cancer and Mesothelioma Patients

More positive results for lung cancer and mesothelioma patients were announced at the European Lung Cancer Conference in Geneva, Switzerland in April. Late last month, Mesothelioma Help reported on the “impressive” results of a mesothelioma clinical trial for the  immunotherapy drug CRS-207 reported at the conference. Now, in another announcement, researchers report the early results of a phase I trial for mesothelioma treatment, combining durvalumab and gefitinib, “shows promise” in lung cancer patients.

Durvalumab, or MEDI4736 from AstraZeneca’s global biologics R&D arm, MedImmune, stimulates the patient’s immune system to attack the cancer and targets the cellular pathway known as PD-1/PD-L1 (proteins found in tumors that can evade detection by the immune system.) Durvalumab blocks the PD-L1 interaction with PD-1.

Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), works by blocking the activity of the EGFR tyrosine kinase enzyme, preventing the growth of new blood vessels that tumors need to grow, and, potentially, killing cancer cells. Iressa (gefitinib) was granted Orphan Drug Designation by the U.S. Food and Drug Administration in August 2014 for the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC).

In a study of 19 patients, 9 patients received concurrent durvalumab and gefitinib and 10 patients received sequential pretreatment with gefitinib followed by the durvalumab/gefitinib combination. After eight weeks, the concurrent treatment group realized an objective response rate of 77.8% and the second group realized an 80.0% objective response rate.

“Reduction in tumor size was observed in all patients treated with gefitinib and durvalumab,” said Don L. Gibbons, MD, PhD, assistant professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, according to an April 15 article on Onclive. “By combining durvalumab with gefitinib, we were looking to attain a more durable response and to delay the development of resistance to gefitinib.”

EGFR is a protein found on the surface of some cells to which epidermal growth factor binds, which causes the cells to divide and spread. It is found at abnormally high levels on the surface of many types of cancer cells. According to a 2009 article in Current Drug Targets, EGFR overexpression has been shown in more than 50% of pleural mesothelioma patients.

Keytruda, another immunotherapy drug targeting PD-L1, has brought new hope to the mesothelioma community with mesothelioma warriors showing excellent results from use of the drug. Mavis Nye of England, who has been participating in a clinical trial for the drug for nearly two years, was told in November that her formerly life-threatening mesothelioma tumors are now dormant. She will receive her last treatment this month.

Pleural mesothelioma is an asbestos-caused cancer of the lining of the lungs. The incurable cancer is highly aggressive and, as a result, is very challenging to treat. Mesothelioma patients are often prescribed the same treatment protocol as lung cancer patients. Progress with immunotherapy combined with other anti-cancer drugs brings hope to the mesothelioma community that survival can be extended with existing treatments.

“These results support potential future investigation of combined durvalumab/gefitinib treatment in NSCLC,” Gibbons said.

To find out more about the clinical trial see ClinicalTrials.gov.

https://clinicaltrials.gov/ct2/results?term=%22malignant+mesothelioma%22&recr=Open&pg=1