Interrupting androgen blockade in men with PCa lowers survival rates
Tuesday, 5 June 2012- Interrupting androgen blockade in men with hormone-sensitive metastatic prostate cancer could shorten their lives, a researcher said here.
In a long-running clinical trial, survival among men given intermittent androgen blockade was inferior to survival in men treated continuously, according to Dr. Maha Hussain, of the University of Michigan Comprehensive Cancer Center in Ann Arbor, Michigan, USA.
Moreover, the survival inferiority was most marked among men with less widespread disease -- the very patients most likely to be offered interrupted treatment, Hussain told reporters at the annual meeting in Chicago of the American Society of Clinical Oncology.
"Continuous therapy continues to be the standard of care," she said. Despite that, interrupted androgen deprivation is widely used in the US, commented Dr. Bruce Roth, of Washington University School of Medicine in St. Louis, who was not part of the study but who moderated a media conference at which details were presented.
That's because the evidence available until now seemed to show the two approaches had the same efficacy, he told MedPage Today. "Doctors didn't have any specific reason (for men) not to come off therapy," he said. "It looked like survival was equivalent."
But the study by Hussain and colleagues is likely to persuade both doctors and patients that sporadic therapy has a dangerous downside, Roth said. "There is a price to pay and that price is nearly 2 years of survival," he said.
The international randomized trial was designed to show that interrupted treatment was not inferior in efficacy to continuous therapy, with an upper bound hazard ratio (HR) of 1.20. "If you can give less treatment while maintaining or improving efficacy and potentially improving the side-effect profile, that would be a clinically important endpoint," Hussain said.
To test the issue, they enrolled 3,040 patients with newly diagnosed metastatic disease and prostate-specific antigen (PSA) level of at least 5 ng/mL of blood.
They were given androgen deprivation therapy for 7 months, using goserelin (Zoladex) and bicalutamide (Casodex), Hussain said. Those who showed a response, defined as a PSA of no more than 4 ng/mL in months six and seven were assigned randomly to continue the therapy or to have it interrupted.
With a median follow-up of 9.2 years, Hussain reported, median overall survival of those in the continuous arm was 5.8 years, compared with 5.1 for those getting intermittent therapy.
The difference yielded an HR for death of 1.09 in favor of continuous therapy, but the upper bound of the 95% confidence interval was 1.24, so that the investigators could not conclude the two were equivalent. When the researchers analyzed subgroups of patients, they found that the intermittent treatment offered equivalent survival in men with extensive disease.
But surprisingly, among men with minimal spread of their cancer, continuous therapy was significantly better, offering a median survival of 7.1 years versus 5.2 for intermittent treatment (HR 1.23, 95% CI 1.02 to 1.49). This was statistically significant at P=0.034, Hussain said.
"We found this rather striking and surprising, as it goes against conventional belief," Hussain said. It may indicate that there are important biological differences between widespread and more limited metastatic prostate cancer, she added.
Source: M. Hussain, et al., "Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic prostate cancer (HSM1PC) patients (pts): Results of S9346 (INT-0162), an international phase III trial," American Society of Clinical Oncology 2012; Abstract 4. MedPage Today