A randomised, double-blind, placebo controlled phase IIB trial shows that treatment with enobosarm, a non-steroidal selective androgen receptor modulator, significantly improved one measure of physical function and increased lean muscle mass in cancer patients overall and specifically in a cohort of patients with non-small cell lung cancer (NSCLC). Dr Christopher Croot of the Department of Hematology and Oncology, North Mississippi Hematology and Oncology Associates, Ltd. Tupelo, USA is a first author of the study which findings were complied in a poster-discussion and presented at the European Multidisciplinary Conference in Thoracic Oncology (EMCTO), held 9-11 May, 2013 in Lugano, Switzerland.
Muscle wasting is a hallmark of cachexia which is caused by byproducts produced by some forms of cancer or by the body's reaction to it. Muscle wasting typically affects skeletal muscles, negatively affecting physical function. It is estimated that more than 50% of lung cancer patients already demonstrate muscle wasting at diagnosis, which increases to affect more than 80% of patients prior to dying from their disease. Enobosarm is non-steroidal selective androgen receptor modulator that is tissue-selective and has anabolic effects in muscle and bone, thus increasing lean body mass.
This randomised, double-blind, placebo controlled study evaluated the effect of enobosarm on lean body mass and physical function in a subset of NSCLC patients. The study enrolled males aged 45 years or more and postmenopausal females, who experienced weight loss of 2% or more over the preceding 6 months. The study participants had been diagnosed with NSCLC, colorectal cancer, non-Hodgkin’s lymphoma, chronic lymphocytic leukaemias, or breast cancer.
The study primary and secondary endpoints were change in lean body mass as determined by dual energy X-ray absorptiometry (DEXA) scan and physical function measured by stair climb power, respectively. Response was defined as either a 10% improvement in stair climb power or no loss in lean body mass.
A total of 159 study participants, including a subset comprised of 61 patients with NSCLC, received enobosarm at doses of 1mg or 3mg or placebo for 16 weeks. At 16 weeks, patients treated with enobosarm achieved statistically significant improvements compared to baseline in stair climb power and lean body mass that were not seen in the patients who received placebo. Among 28 NSCLC patients who were evaluable for stair climb power, 18 enobosarm treated subjects showed an improvement of median 17% over baseline that was statistically significant (p=0.007). Among the 31 NSCLC subjects who were evaluable for lean body mass, the enobosarm cohort of 21 patients showed a median 1.0 kg increase in lean body mass; whereas, a 0.8 kg loss of lean body mass was observed in patients receiving placebo. The responder analysis demonstrated that 78% and 67% of enobosarm treated patients met the criteria defining stair climb power and lean body mass response, respectively.
Enobosarm was well tolerated and commonly reported adverse events were consistent with adverse events seen with chemotherapy and included fatigue, anaemia, nausea, and diarrhoea.
On Friday April 12, 2013, an independent Data Safety Monitoring Board (DSMB) announced that a per protocol safety review of unblinded safety data supported the two pivotal phase III clinical trials of enobosarm that are ongoing to determine the prevention and treatment of muscle wasting in patients with advanced NSCLC.
During the time foreseen for questions and answers, the first author of the study said that two ongoing phase III studies evaluate enobosarm with different type of chemotherapy, one investigate platinum and taxane-based chemotherapy, while the second evaluate platinum and non-taxane regimen. It is important because it is well known that chemotherapy itself can treat symptoms in patients with NSCLC. Each of these phase III studies enrolled 320 patients. The last patient has been enrolled last week. The second point raised during the discussion was that the study authors did not prospectively investigate on the use of glucocorticoids. It would be also important in such studies to test androgen receptor in tumour tissue, however the study presenter said that it has been for a long time speculated on role of testosterone and more lung cancer rates in men than in women, however he doesn't believe the androgen receptor has a major impact on the outcome in NSCLC.
EMCTO is organised in partnership between the European Society for Medical Oncology (ESMO), The European Society for Radiotherapy and Oncology (ESTRO), the European Society of Thoracic Surgeons (ESTS) and the European Respiratory Society (ERS), and the European Thoracic Oncology Platform (ETOP). The five partners have created a programme that integrated perspectives from the different disciplines and demonstrated how the multidisciplinary team can combine knowledge for personalised treatment of the whole range of thoracic oncology tumours.
Authors MA Johnston disclosed that he is an employee and owns stock in GTx, Inc.; MS Steiner disclosed that he is the CEO and Chairman of the Board of GTx, he and his family own stock in GTx, Inc.; and ML Hancock is employee and own stock with GTx.