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Abiraterone acetate offers no survival advantage over docetaxel for prostate cancer
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MADRID — Abiraterone acetate with prednisone provided no significant difference in OS compared with docetaxel for men with high-risk prostate cancer beginning long-term hormone therapy, according to results of the STAMPEDE trial presented at the European Society for Medical Oncology Congress.
“Oncologists and urologists want to know which combination is preferable, which is why we conducted this opportunistic analysis,” Matthew Sydes, MSc, statistician with the Medical Research Council Clinical Trials Unit at University College London, said during his presentation. “This comparison was underpowered, but it is the only data we have to directly compare docetaxel and abiraterone in this setting.”
Androgen deprivation therapy had been standard for men with locally advanced or metastatic prostate cancer since the 1940s. However, docetaxel with ADT became the new standard in 2015 after results from the CHAARTED study appeared in The New England Journal of Medicine.
That study showed six cycles of docetaxel — an IV chemotherapy — improved median OS from 44 months to 57.6 months compared with ADT alone.
Two studies presented at this year’s ASCO Annual Meeting showed abiraterone acetate (Zytiga, Janssen) — an oral adrenal inhibitor — also improved survival compared with ADT alone.
The LATITUDE study, based on median follow-up of 30 months, showed the addition of abiraterone and prednisone to ADT more than doubled median time to progression from 14.8 months to 33 months.
The STAMPEDE trial, based on median follow-up of 40 months, showed the addition of abiraterone acetate to ADT reduced risk for death by 37% among men with high-risk prostate cancer.
The subanalysis that Sydes presented at ESMO included 566 men (median age, 66 years) randomly assigned to ADT plus abiraterone and prednisone (n = 377), or to ADT plus docetaxel (n = 189). Groups appeared well balanced for disease stage (60% M1), Gleason score (76% Gleason 8 to 10) and WHO performance status.
At median follow-up of 4 years, 111 deaths occurred in the ADT/abiraterone/prednisone group and 45 deaths occurred in the ADT/docetaxel group (HR for OS = 1.16; 95% CI, 0.82-1.65).
Estimates of other early outcome measures clearly favored abiraterone, including failure-free survival (HR = 0.51; 95% CI, 0.39-0.67) and PFS (HR = 0.65; 95% CI, 0.48-0.88).
Estimates of late outcome measures, such as freedom from metastases-free survival (HR = 0.77; 95% CI, 0.57-1.03) and freedom from symptomatic skeletal events (HR = 0.83; 95% CI, 0.55-1.25), also favored abiraterone; however, the differences between treatment groups did not reach statistical significance.
“We see strong evidence for abiraterone in terms of its early outcome measures, we see weak evidence for abiraterone for metastatic progression-free survival, and we see no evidence of difference in skeletal ischemic events, cause-specific survival and overall survival,” Sydes said.
Researchers reported no significant differences between treatment groups for grade 3 toxicity (40% for ADT plus abiraterone/prednisone vs. 36% for abiraterone plus docetaxel), grade 4 toxicity (7% vs. 13%) or grade 5 toxicity (1% each).
Cora N. Sternberg, MD, chief of medical oncology at San Camillo Forlanini Hospital in Rome, called the STAMPEDE trial “very innovative” and noted that the common toxicities associated with abiraterone — which include high blood pressure, low potassium level or liver enzyme abnormalities — were favorable compared with docetaxel, which can cause nausea, constipation, diarrhea, neutropenia or fatigue.
“Toxicities associated with chemotherapy for six cycles will dominate decisions about upfront docetaxel,” Sternberg said. “Toxicities associated with abiraterone are also likely to influence decisions. Physicians will base their choice of therapy on availability and patient characteristics and preferences.”
Cardiovascular follow-up will be important for patients taking abiraterone, Sternberg said.
One ongoing randomized trial is evaluating darolutamide (ODM-201; Orion, Bayer HealthCare) in combination with docetaxel, and another is evaluating abiraterone in combination with docetaxel. The results of these trials could alter the standard of care for men with metastatic hormone-sensitive prostate cancer. – by Chuck Gormley
Reference:
Sydes M, et al. Abstract LBA31_PR. Presented at: European Society for Medical Oncology Congress; Sept. 8-12, 2017; Madrid.
Disclosures: Cancer Research UK, Medical Research Council, Janssen, Astellas, Clovis Oncology, Novartis, Pfizer and Sanofi funded this study. Sydes reports grants and nonfinancial support from Janssen, Astellas, Clovis Oncology, Novartis, Pfizer and Sanofi. Please see abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Nicholas D. James, MBBS, PhD
It is quite interesting to have head-to-head comparisons of abiraterone and docetaxel. If you look at the HRs of the docetaxel trials and abiraterone trials, you think abiraterone is obviously better. As it turns out, for survival and skeletal-related events, there’s absolutely no difference. They’re both very good, in fact.
We have quality of life data as well, which is very interesting. We just analyzed our docetaxel quality-of-life data and, although we haven’t published it yet, basically docetaxel improves quality of life in much the same way abiraterone improves quality of life.
In the United Kingdom, we can use docetaxel but we can’t use abiraterone. These results mean, in all honesty, I can sit in clinic and tell my patients: “Sir, you cannot have (abiraterone) but you can have (docetaxel), and it will keep you alive just as long.” That is the bottom-line, take-home message.
If I had both (abiraterone and docetaxel) available to me, it’s more a sequencing question than an either/or question. In my opinion, you would get both, and I’d suggest it doesn’t matter which order you get them. In truth, if a patient is faced with taking pills or taking chemotherapy, he will always say, “I’ll take pills.” If you say, “Do you want to take pills now and chemotherapy later,” or “Chemotherapy now and pills later,” they’re not quite sure. Maybe they take the bad stuff and get it out of the way first.
Either way, I suspect there will be some degree of additional benefit from both. I think that’s probably where it will end up within a year or so. We’ll give docetaxel and then we’ll give abiraterone after. We’re about to test PARP inhibitors in the STAMPEDE trial, and we’re just setting up sequencing in newly diagnosed mutations. That will open in the next few weeks.
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