1. Fuerst, Mark L.

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CHICAGO-Early use of abiraterone acetate plus prednisone added to standard hormonal therapy can significantly improve survival among men with newly diagnosed high-risk, metastatic prostate cancer, according to a new study.

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In a large phase III clinical trial, the combination significantly improved overall survival with a 38 percent reduction in the risk of death and more than doubled the median time until cancer progression.


"These findings indicate that the addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) can potentially be considered a new standard of care for patients with high-risk, newly diagnosed metastatic prostate cancer," said lead author Karim Fizazi MD, PhD, Head of the Department of Cancer Medicine at Gustave Roussy, University Paris-Sud in Villejuif, France, at a press briefing at the 2017 ASCO Annual Meeting, held June 2-6.


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, Fizazi noted. "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 at all," he explained.


Patients with newly diagnosed metastatic hormone-naive prostate cancer, particularly those with high-risk characteristics, have a poor prognosis. ADT plus docetaxel has been shown to improve outcomes in these patients, "but many patients are not candidates for docetaxel and may benefit from alternative therapy," according to Fizazi, who noted that abiraterone acetate plus prednisone is indicated for metastatic castration-resistant prostate cancer patients.


Abiraterone stops 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 ADT.


LATITUDE Study Findings

Fizazi reported the interim results of LATITUDE, which is a multinational, randomized, placebo-controlled, phase III clinical trial of men with newly diagnosed, high-risk metastatic prostate cancer who had not previously received ADT (Abstract LBA3). All patients 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.


The patients were randomly assigned to receive ADT plus abiraterone 1 gm daily plus prednisone 5 mg daily or ADT plus placebo. Prednisone is routinely given with abiraterone to manage certain side effects of abiraterone, such as low potassium or high blood pressure.


Co-primary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS). One rPFS, two interim, and one final OS analyses were planned. At this first interim analysis after a median follow-up of 30.4 months, there were 406 deaths and 593 rPFS events. Because OS, rPFS, and all secondary endpoints significantly favored ADT plus abiraterone acetate plus prednisone, the Independent Data Monitoring Committee unanimously recommended unblinding the study and crossing patients over to this combination.


Men who received abiraterone had a 38 percent lower risk of death than those who received placebo. The median OS had not yet been reached in the abiraterone group-more than 50 percent of patients in that group were still alive at the time of the interim analysis, so a median survival could not be calculated. Median OS was 34.7 months in the placebo group.


The median OS was 66 percent in the ADT plus abiraterone acetate and ADT plus placebo.


The abiraterone group was also associated with a 53 percent lower risk of progression than the placebo group and resulted in delayed cancer growth by a median of 18.2 months.


Several severe side effects were more common with abiraterone acetate and prednisone than placebo: high blood pressure (in 20% vs. 10% of men), low potassium level (10.4% vs. 1.3%), and liver enzyme abnormalities (5.5% vs. 1.3%). "We need to be cautious when using abiraterone in men who have an increased risk for heart problems, such as those with diabetes," stated Fizazi.


He added, "we had been treating metastatic prostate cancer the same way for 70 years until docetaxel chemotherapy was shown to improve survival in 2015. Now in 2017, we show abiraterone is also helping patients live longer."


The next step is to see whether adding abiraterone on top of docetaxel offers further benefit, Fizazi concluded, noting that this study is currently ongoing in Europe.


Mark L. Fuerst is a contributing writer.