ETOP/EORTC trial to evaluate denosumab for treating patients with advanced non-small cell lung cancer

Lung cancer is currently the main cause of cancer related death among both men and women. In fact, there were an estimated 409,900 new cases and an estimated 353,500 deaths due to lung cancer in Europe in 2012. Of all lung cancer types, non-small cell lung cancer (NSCLC) accounts for 85%, and for advanced disease stages survival rates are quite poor. Moreover, nearly half of all lung cancer patients develop bone metastases, and these contribute not only to the high morbidity rate but to skeletally related events such as fractures and spinal cord compression that adversely affect quality of life. Improved treatments are sorely needed for these patients.

The ETOP 5-12/EORTC 08111 – SPLENDOUR (Survival imProvement in Lung cancEr iNduced by DenOsUmab therapy) trial will evaluate the addition of denosumab to standard first-line anticancer treatment in advanced NSCLC. It is thought that denosumab, by binding to the receptor activator of the nuclear factor-KappaB ligand, a protein that triggers bone removal, might help control skeletal related events and would eventually improve survival in NSCLC patients. This drug is already approved for postmenopausal women with osteoporosis, prevention of bone complications in patients with bone metastases from solid tumors, and treatment of patients with giant cell tumor of the bone.

Dr. Sarah Danson of the Sheffield Teaching Hospitals NHS Foundation Trust – Weston Park Hospital and EORTC coordinator of this study says, “Adding denosumab to the standard first line treatment for patients with non-small cell lung cancer could improve their overall survival. In this study we plan to enroll 1000 patients with untreated advanced NSCLC, performance status 0-2, both with and without bone metastases at diagnosis. Patients will be randomized to receive standard platinum based chemotherapy combined with pemetrexed or gemcitabine or experimental arm where in addition to standard chemotherapy patients will also be administered denosumab every three to four weeks.”

The primary endpoint of the ETOP 5-12/EORTC 08111 trial is overall survival. Secondary endpoints include progression-free survival and response based on RECIST 1.1, the toxicity profile of denosumab assessed and graded according to version 4 of the United States National Cancer Institute Common Terminology Criteria for Adverse Events, and the evaluation of potential predictive markers for denosumab activity.

The randomized open-label phase III ETOP 5-12/EORTC 08111 SPLENDOUR trial is sponsored by the European Thoracic Oncology Platform and coordinated by the EORTC Lung Cancer Group in collaboration with the Central European Cooperative Oncology Group. This trial is supported by an educational grant from Amgen and will be conducted in 70 sites in 14 countries: Austria, Belgium, Bulgaria, France, Germany, Israel, Italy, Poland, Republic of Ireland, Romania, Slovenia, Spain, Switzerland and the United Kingdom. Sites in France, Spain and Switzerland have already opened, and the first patients have already been enrolled.

John Bean, PhD
EORTC, Medical Science Writer