A randomised, double-blind, placebo controlled phase IIB trial has shown that treatment with Enobosarm, a non-steroidal selective androgen receptor modulator, significantly has 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 ).
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-Hodgkins 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 non-small cell lung cancer, 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.
Source: European Multidisciplinary Conference in Thoracic Oncology ( EMCTO ), 2013