乌鸦传媒

CHICAGO -- Dramatic results in two clinical trials are persuading experts here that an androgen-suppressing drug should be used earlier in men with prostate cancer.

Abiraterone acetate (Zytiga), combined with prednisone, is approved to treat men whose prostate cancer no longer responds to androgen deprivation therapy (ADT), so-called metastatic castration-resistant disease.

But in men newly diagnosed with the disease, adding the drug to standard ADT markedly decreased the risk of death and disease progression, investigators on the two studies told reporters at the American Society of Clinical Oncology annual meeting.

The findings come just a few years after the treatment of newly diagnosed prostate cancer was revolutionized by the addition of chemotherapy with docetaxel to the standard hormone therapy, commented ASCO expert Sumanta Kumar Pal, MD, of City of Hope in Duarte, Calif.

But the abiraterone combination "mirrors or exceeds" the benefit seen with docetaxel with far fewer side effects, Pal said, adding that it should be a new standard of care -- at least in men with metastatic disease at diagnosis. The studies, while very different, had "congruent" results, which lend confidence to their findings, he added.

In the LATITUDE study, investigators tested the drug combination (AA-P) in men newly diagnosed with prostate cancer that had already metastasized, according to Karim Fizazi, MD, PhD, of Gustave Roussy hospital in Villejuif, France.

In the long-running study, investigators also included men with non-metastatic disease, according to Nicholas James, MD, of the University of Warwick and Queen Elizabeth Hospital in Birmingham, England. The results appear simultaneously in the .

Despite the differences, both studies showed nearly a 40% reduction in the risk of death.

The LATITUDE investigators enrolled 1,199 men with at least two of three risk factors (Gleason score of 8 or more, at least three bone lesions, or measurable visceral metastases) and randomly assigned them to either AA-P plus standard ADT or standard treatment plus a placebo.

The co-primary endpoints of the trial were overall survival (OS) and radiographic progression-free survival (PFS), Fizazi said, and in a planned interim analysis after a median follow-up of 30.4 months, both were improved with the addition of AA-P.

He reported that 66% of those in the experimental arm and 49% of those in the control arm remained alive after 3 years, for a hazard ratio of 0.62. The median survival for standard therapy plus placebo was 34.7 months but was not yet reached for the AA-P arm.

Radiographic PFS was 33 months for the AA-P arm and 14.8 months for the control arm (HR 0.47).

Fizazi said the treatment also met all of the study's secondary efficacy endpoints, including such measures as time to pain progression and time to symptomatic skeletal events.

Because of the efficacy, the study's data monitoring committee recommended halting the trial and offering the AA-P combination to all patients, he stated.

But Fizazi added that doctors using the combination will have to be careful about possible adverse events: some 20.3% of patients getting AA-P developed hypertension, compared with 10% of those in the control arm; 10.4% and 1.3% developed hypokalemia; 5.5% had increased alanine aminotransferase (ALT) compared with 1.3%; and 4.4 had elevated aspartate aminotransferase (AST) versus 1.5%.

The STAMPEDE trial is a multi-arm, multi-stage trial designed so that different interventions can be tested in a sequential fashion; the trial was one of three that demonstrated the value of docetaxel chemotherapy plus ADT in metastatic but hormone-sensitive prostate cancer.

For this analysis, the researchers enrolled 1.917 newly diagnosed patients -- 52% of them with metastatic disease -- and randomly assigned them to standard ADT plus AA-P for 2 years or disease progression.

The primary endpoint was death from any cause, although the researchers also looked at failure-free survival, James said.

After 40 months, 262 men in the standard therapy group had died, compared with 184 in the abiraterone group, yielding 3-year overall survival rates of 83% and 76%, respectively. The HR for death was o.63

James said abiraterone lowered the relative chance of treatment failure (defined as clinical, radiologic, or prostate-specific antigen progression or death from prostate cancer) by 71% compared with standard therapy.

Hormone therapies have been getting better, so "these studies are actually not a great surprise to me," commented Otis Brawley, MD, of the American Cancer Society,

But Brawley, who was not involved in the studies, cautioned that all such drugs have the potential for serious harm, including cardiac disease and even progression of the prostate cancer.

"We have to realize that these drugs that we use to treat prostate cancer are double-edged swords," Brawley said. "We need to use these drugs very carefully."