In my continuing reports about interesting and pertinent information released at the ASCO 2014 meeting one abstract described a phase 2 trial combining an attack on androgens in metastatic prostate cancer resistant to initial hormone therapy. This proof of concept study showed that combining Enzalutamide (Xtandi) plus abiraterone (Zytiga) drove down testosterone levels and appeared safe.
They found that Enzalutamide (Xtandi) plus abiraterone (Zytiga) dropped blood and bone marrow androgens down to undetectable levels for 80% of men, reported by Eleni Efstathiou, MD, PhD, of the MD Anderson Cancer Center in Houston.
The trial looked at the Pharmacokinetics of the combination of these two new drugs and the results suggested no meaningful negative interactions for either drug on the other, suggesting both can be used at full dose.
“We believe the combination can be developed safely,” Efstathiou said.
According to Mary-Ellen Taplin, M.D. of the Dana-Farber Cancer Institute in Boston and discussant at the meeting, “There’s been ample evidence that androgen receptor remains signaling in these patients,” she noted. “So it makes sense that perhaps we should target it more intensely.”
The dual approach was expected to block feedback mechanisms in androgen signaling, tackling both biosynthesis and receptors, Efstathiou explained.
This trial was a single arm, phase 2 trial that included 60 men with progressive castration-resistant prostate cancer metastatic to bone who had serum testosterone levels at entry of less than 50 ng/dL. All of the subjects had at least one prior line of ADT, but the range was up to four.
The subjects received enzalutamide at 160 mg once daily, abiraterone 1g once daily, and prednisone 5 mg twice daily.
The researchers have reported that no new safety concerns not previously associated with these drugs arose during the trial. Despite this, there was an increase in toxicity, Taplin said, pointing to the 73% rate of grade 1 to 3 fatigue compared with 36% in the PREVAIL trial with enzalutamide and a 40% increase over the COUGAR 302 trial of abiraterone.
There is a larger phase 3 trail currently being conducted. We now need to wait for this trial result before we can safely allow these drugs to be used in combination in the clinic.
The results as reported at ASCO and in this post come only from an abstract and a presentation at the meeting. Until the results are published in a peer reviewed article they shouls only be considered as being preliminary.
Joel T. Nowak, M.A., M.S.W.