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Abiraterone acetate with prednisone reduces risk for prostate cancer death
CHICAGO — The addition of abiraterone acetate with prednisone to standard hormonal therapy led to a 38% lower risk for death in men with high-risk, metastatic prostate cancer, according to results of the phase 3 LATITUDE trial presented at the ASCO Annual Meeting.
Abiraterone acetate (Zytiga, Janssen) also more than doubled the median time to prostate cancer worsening, from 14.8 months to 33 months, researchers reported.
“There is a large unmet need to improve treatment for men with newly diagnosed metastatic cancer, who die of the disease within less than 5 years on average,” Karim Fizazi MD, PhD, head of the department of cancer medicine at Gustave Roussy, University Paris-Sud in Villejuif, France, said during a press briefing. “The benefit from early use of abiraterone we saw in this study is at least comparable to the benefit from docetaxel chemotherapy, which was observed in prior clinical trials, but abiraterone is much easier to tolerate, with many patients reporting no side effects.”
Prostate cancer growth is fueled by testosterone. Abiraterone stops the production of testosterone throughout the body by blocking an enzyme that converts other hormones to testosterone. The FDA previously approved abiraterone for patients with metastatic prostate cancer that worsened despite androgen deprivation therapy (ADT).
LATITUDE is a multinational, randomized placebo-controlled phase 3 clinical trial of 1,200 men with newly diagnosed, high-risk metastatic prostate cancer who had not previously received ADT. All trial participants had at least two of three risk factors:
- Gleason score of 8 or more;
- three or more bone metastases; or
- three or more visceral metastases
Researchers randomly assigned patients to receive ADT plus abiraterone and prednisone, or ADT plus placebo. Patients routinely receive corticosteroid prednisone along with abiraterone to manage its side effects, such as low potassium or high blood pressure.
OS and radiographic PFS served as primary endpoints.
After median follow-up of 30.4 months, 406 deaths (48%) and 593 radiographic PFS events had occurred.
Men who received abiraterone demonstrated a 38% lower risk for death than those who received placebo (HR = 0.62; 95% CI, 0.51-0.76).
Median OS had not yet been reached in the abiraterone group, as more than 50% of men in that group remained alive at the time of analysis. Researchers reported median OS of 34.7 months in the placebo group.
Abiraterone conferred a 53% lower risk for radiographic PFS (HR = 0.47; 95% CI, 0.39-0.55) and resulted in cancer growth being delayed by a median of 18.2 months.
“We had been treating metastatic prostate cancer the same way for 70 years until docetaxel chemotherapy was shown to improve survival in 2015, and now in 2017 we show abiraterone is also helping patients live longer,” Fizazi said.
Severe side effects that appeared more common with abiraterone acetate and prednisone included high blood pressure (20% vs. 10%), low potassium level (10.4% vs. 1.3%) and liver enzyme abnormalities (5.5% vs. 1.3%).
Abiraterone is used in combination with the steroid prednisone to help minimize the risk of hypertension, Fizazi said.
“What we learned about abiraterone is that is better tolerated than docetaxel,” Fizazi said. “Having 6 months of grade 1 or grade 2 diarrhea [with docetaxel] is horrible. Two years of grade 1 or grade 2 fatigue is really bad. We don’t see that with abiraterone. Basically, what we’re fearing with this drug is high hypertension that can be dangerous. We need to be cautious when using abiraterone in men who have an increased risk for heart problems, such as those with diabetes.”
Researchers in a European study are analyzing whether adding abiraterone to docetaxel chemotherapy offers further benefit. – by Chuck Gormley
Reference:
Fizazi K, et al. Abstract LBA3. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: Janssen Research and Development funded this study. Fizazi reports consultant or advisory roles with Astellas, AstraZeneca, Bayer, Clovis Oncology, Curevac, ESSA, Janssen, Orion Pharma GmbH and Sanofi; travel expenses from Amgen; and honoraria from Amgen, Astellas, Janssen, Merck, Sanofi and Takeda. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
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Hormone therapy has been a mainstay in treatment for metastatic prostate cancer for decades. At the ASCO Annual Meeting in 2014, the treatment paradigm for prostate cancer was shaken up by an NCI–sponsored study called TRIAL, which showed a survival benefit associated with the addition of chemotherapy with hormone therapy. The addition of chemotherapy to the treatment of prostate cancer is no small feat, because toxicity associated with chemotherapy is a concern. The data from Fizazi and colleagues provides an important alternative to chemotherapy, namely the use of abiraterone. Abiraterone inhibits testosterone production more potently than hormone therapies previously used in this setting. Although it’s challenging to put the existing data for chemotherapy and abiraterone side by side, at first glance it appears as though the benefits of survival seen with abiraterone mirror or exceed the benefit we’ve seen with chemotherapy. Chemotherapy brings with it significant toxicities like neurodamage, fatigue and decreases in blood counts, which are often very difficult for patients to handle. By and large, what we’re finding is that many patients will decline the use of docetaxel after a thorough discussion of side effects. That emphasizes the importance of these abiraterone data sets. I find in my discussions with patients regarding abiraterone, there’s a much higher tendency to accept the side-effect profile involved in this therapy. That’s going to be a major driver in the change in pattern of utilization. Abiraterone brings the same level or greater level of effectiveness against prostate cancer with far fewer side effects. These advances should immediately reshape our treatment algorithms for prostate cancer, and abiraterone with conventional hormone therapy should become a new standard of care for men with high-risk metastatic prostate cancer. The investigative community will have to focus on determining whether there remains a role for chemotherapy in this setting for selected patients.