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Addition of abiraterone to androgen deprivation reduces risk for death in advanced prostate cancer
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CHICAGO — The addition of abiraterone acetate to standard initial treatment reduced the risk for death among men with high-risk advanced prostate cancer by 37%, according to results of the STAMPEDE trial presented at the ASCO Annual Meeting.
The combination of abiraterone acetate (Zytiga, Janssen) and androgen deprivation therapy (ADT) improved the 3-year survival rate from 76% to 83%, reduced the risk for relapse by 70% and reduced the risk for serious bone complications by 50%.
“Our projections are that, in the metastatic arm of prostate cancer survivors, survival can improve from 3.5 years to 6.5 years with abiraterone,” Nicholas James, BSc, MBBS, PhD, professor of clinical oncology at Queen Elizabeth Hospital in Birmingham, United Kingdom, said during a press briefing. “We think this is one of the biggest improvements ever recorded in a trial of this magnitude. We also feel this survival data applies to the whole prostate cancer population and not just the metastatic arm.”
ADT slows prostate cancer growth by preventing testicles from making testosterone and other similar hormones. Despite ADT, other organs in the body — including the prostate gland — continue to make small amounts of testosterone and other androgens. Abiraterone stops production of both testosterone and other androgens throughout the body by targeting an enzyme that converts other hormones to androgens.
In the STAMPEDE trial — an ongoing multi-arm, multistage randomized clinical trial conducted in the United Kingdom and Switzerland — researchers compared standard therapy with or without abiraterone in 1,917 men with high-risk prostate cancer who were starting ADT. All men had either locally advanced or metastatic cancer, and all were beginning long-term standard ADT for the first time. Nearly half (48%) of men in the study population had locally advanced cancer, and they were eligible to receive radiation therapy in addition to ADT.
At median follow-up of 40 months, 262 deaths had occurred among those assigned standard therapy and 184 deaths had occurred among those assigned abiraterone.
Researchers reported 3-year OS of 83% in the abiraterone group and 76% in standard therapy group. Abiraterone reduced the relative chance of treatment failure — measured by worsening scans or symptoms, or elevated PSA level — by 71% compared with standard therapy.
Incidence of adverse effects appeared similar between the two groups, although severe side effects occurred more frequently in the abiraterone group (41% vs. 29%). The most common adverse effects that occurred among abiraterone-treated patients included high blood pressure and liver problems. Two treatment-related deaths occurred in the abiraterone group and one occurred in the standard therapy group.
“With docetaxel, you get 15 weeks of treatment and it’s over,” James said. “With abiraterone, you’re looking at a treatment over a much longer time period — the average duration for patients with metastatic disease is 33 months — so comparing [adverse events between] abiraterone with docetaxel is apples and oranges. ... It is possible that certain patients who have a fast-growing cancer might benefit from a combination of abiraterone and docetaxel, but we need more research to confirm that.” – by Chuck Gormley
Reference:
James N, et al. Abstract LBA5003. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure:
Cancer Research UK, Medical Research Council and Janssen funded this study, with additional contributions to the STAMPEDE protocol from Astellas, Clovis Oncology, Janssen, Novartis, Pfizer and Sanofi. James reports consultant roles with Astellas, Bayer, Janssen, Merck and Sanofi; travel, accommodations and expenses from Sanofi; honoraria from Astellas, Bayer, Janssen, OncoGeneX, Pierre Fabre and Sanofi; and research funding from Astellas, Janssen, Novartis, Pfizer and Sanofi. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Sumanta Kumar Pal, MD
This is a highly unique treatment paradigm where arms of the study are essentially married on top of one another, allowing us to rapidly build on existing standards. Several years ago, the STAMPEDE trial actually showed the benefits associated with chemotherapy and conventional hormone therapy for metastatic prostate cancer. In the LATITUDE study, the same study background is used to show the benefit of abiraterone acetate (Zytiga, Janssen). Its remarkable to see the similarities in survival benefit across the two studies in the metastatic populations, but the key differences in the STAMPEDE study is the inclusion of patients with nonmetastatic disease. Although Dr. James sees the degree of benefit in survival as similar in nonmetastatic and metastatic patients, I would argue that further study is needed to determine candidates for abiraterone for patients with nonmetastatic disease. The confidence interval for abiraterone straddles 1 and that, to me, suggests we havent completely defined the benefit of abiraterone in that population. These issues notwithstanding, abiraterone should change the treatment paradigm for patients with newly diagnosed metastatic prostate cancer and largely displaces chemotherapy as standard therapy.
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David M. Nanus, MD
The standard therapy that has been around since the 1950s for metastatic prostate cancer is androgen deprivation therapy — also known as hormonal therapy or testosterone-lowering therapy. Patients typically go into remission for years before the prostate cancer starts progressing, despite the absence of circulating testosterone. Researchers discovered a few years ago that there are many mechanisms by which the cancer cells can evade this lack of circulating testosterone. For instance, prostate cancer cells can acquire the ability to make their own testosterone and abiraterone acetate (Zytiga, Janssen) inhibits specific enzymes in this pathway, shutting down testosterone synthesis. Abiraterone has been previously shown to be effective in patients that progress despite low levels of circulating testosterone. Over the past few years, studies have shown that in patients with newly diagnosed metastatic prostate cancer, the addition of six cycles of docetaxel chemotherapy prolongs how long patients live. The studies reported at ASCO show that the addition of abiraterone to ADT also prolongs survival in newly diagnosed patients with metastatic prostate cancer. What makes this approach a new paradigm is that a patient does not have to come in for a chemotherapy infusion, but can have a similar benefit taking an oral pill. The standard of care will change, in part because of less toxicity and greater ease for patients compared with chemotherapy. It also raises the question about triple therapy with ADT, abiraterone and docetaxel. Will this translate into more cures? It certainly seems like this approach will improve survival, resulting in patients dying with prostate cancer and not of prostate cancer. This is practice changing.
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