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Docetaxel improves survival for men with hormone-naive prostate cancer
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The addition of docetaxel to standard therapy clinically and significantly improved survival for men with locally advanced or metastatic hormone-naive prostate cancer, according to findings from the STAMPEDE trial.
However, the addition of zoledronic acid to standard therapy was not associated with improved survival, results showed.
“We hope our findings will encourage doctors to offer docetaxel to men newly diagnosed with metastatic prostate cancer, if they are healthy enough for chemotherapy,” Nicholas David James, MD, PhD, director of the cancer research unit at the University of Warwick and consultant in clinical oncology at Queen Elizabeth Hospital in the United Kingdom, said in a press release. “Men with locally advanced, nonmetastatic prostate cancer may also consider docetaxel as part of upfront therapy, as it clearly delays relapse.
“It’s also clear that zoledronic acid does not benefit these patients and should not be offered as an upfront treatment for advanced prostate cancer,” James said.
The ongoing STAMPEDE trial — the largest randomized trial of men with prostate cancer to date (n ˃ 6,500) — has multiple stages and arms and can be adapted to assess new therapies as well as changes to the standard of care, according to study background. As the trial progresses, ineffective treatment arms are stopped and new arms are added to determine efficacy and safety of emerging treatments.
James and colleagues evaluated data from 2,962 hormone-naive men from four of the study’s nine arms. These four arms assessed standard of care — a minimum of 3 years of androgen deprivation therapy plus localized radiation for suitable patients — alone, standard of care plus docetaxel for six cycles, standard of care with zoledronic acid for 2 years, and standard of care with docetaxel and zoledronic acid.
The groups were well balanced with regard to patient characteristics. The median age of the population was 65 years. Sixty-one percent of the patients had metastatic disease and 93% were diagnosed within 6 months prior to randomization.
Median follow-up was 42 months.
Median OS was 77 months in the standard of care plus docetaxel arm and 67 months in the standard of care alone arm. Docetaxel was associated with a 24% reduction in the risk for death compared with standard of care alone (HR = 0.76; 95% CI, 0.63-0.91).
There was a 22-month OS improvement associated with the addition of docetaxel to standard of care in the subset of patients with metastatic disease (65 months vs. 43 months). Docetaxel extended time to relapse by 38% for all patients.
Researchers calculated HRs of 0.93 (95% CI, 0.79-1.11) for standard of care plus zoledronic acid and 0.81 (95% CI, 0.68-0.97) for standard of care plus docetaxel and zoledronic acid vs. standard of care alone.
More patients assigned docetaxel with standard of care experienced a grade 3 to 5 adverse event compared with patients assigned standard of care alone (50% vs. 31%). However, the researchers noted toxicities were manageable and very few patients discontinued docetaxel due to adverse events.
“Docetaxel should be considered a routine practice in men with newly diagnosed, metastatic disease,” James said during a press conference. “For nonmetastatic disease there remains uncertainty as to whether there is a survival benefit, but it certainly improves failure-free survival by a substantial amount” – by Anthony SanFilippo
Reference:
James ND, et al. Abstract 5001. Scheduled for presentation at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Disclosure: The study was funded in part by Astellas, Janssen, Novartis, Pfizer and Sanofi-Aventis. The researchers report travel expenses, research funding and honoraria from and speakers bureau, consultant/advisory roles and other financial relationships with Astellas, Bayer, Bristol-Myers Squibb, Dendreon, Ferring, FirstWord, GlaxoSmithKline, Janssen, Janssen-Cilag, Lilly, Merck, Novartis, OncoGeneX, Pfizer, Pierre Fabre, Roche, Sanofi and Takeda.
Perspective
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Peter Paul Yu, MD, FACP, FASCO
It is important to put this into a broader context about how we approach men with prostate cancer who very often are more elderly when they develop prostate cancer. The paradigm for years, or even decades, has been to treat these men with hormone therapy because hormone therapy is relatively less-toxic, although it has significant side effects in terms of fatigue, anemia and other problems. The bias has been to use hormone therapy until it is exhausted, until there is no response left, and then at the last moment, use chemotherapy. This is often a self-defeating strategy, because you are using chemotherapy when the disease has evolved to a point where it is much more aggressive.
Last year at the ASCO plenary session, we began to see evidence that this might be the wrong strategy for some men. Giving chemotherapy up front with the hormone therapy might be better than hormone therapy followed by chemotherapy only at the last stages.
This is a much larger study than we have previously seen. It continues to add increasing evidence that adding chemotherapy early on prolongs survival in men and we’ve had this chemotherapy drug that has been around for quite a long time. We know that it is tolerable by men as a single-agent treatment. So, this is not a treatment that is very difficult to take. This paradigm shift is continuing and should be highlighted.
The real interesting thing is that there is a very strong hint that this strategy of bringing chemotherapy early on can have the benefit even in men who do not have evidence of metastases at the time they are starting hormone therapy. This is traditionally what we would call the adjuvant use of chemotherapy. This is typically what we have seen with adjuvant therapy — first you show a benefit in metastatic disease then you start to use that agent earlier and you see more and more benefit. We are starting to see this evolution toward nonmetastatic disease as well.
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