The next step for the research would be to determine whether adding abiraterone to docetaxel and ADT further improves outcomes, said Fizazi, who is head of the department of cancer medicine at Gustave Roussy, University Paris-Sud in Villejuif, France.
LATITUDE Study Findings
The multinational LATITUDE trial enrolled men who had not previously received ADT therapy and had at least 2 of 3 risk factors: Gleason score greater than or equal to 8, measurable visceral metastases, or 3 or more bone lesions. Results presented at the conference were from the first interim analysis involving 1199 patients: 597 in the abiraterone arm and 602 in the control group.
Patients with newly diagnosed metastatic disease live less than 5 years on average, Fizazi said. He said this category includes 3% to 5% of patients in the United States and other Western countries, and rises as high as approximately 60% of newly diagnosed patients in some Asian countries.
The co-primary endpoints for the study were OS and radiographic PFS. Based on results thus far, the International Data Monitoring Committee has unanimously recommended unblinding the study and allowing patients to cross over to the abiraterone arm.
After a median follow-up of 30.4 months, the median overall survival (OS) had not yet been reached (NR) in the abiraterone arm; the median OS in the control group was 34.7 months (HR, 0.62; 95% CI, 0.51-0.76; P
<.0001). The OS rate at 3 years was 66% in the abiraterone group versus 49% with placebo.
The abiraterone-containing regimen also has been shown to significantly improve secondary endpoints compared with the control group in the time to pain progression (NR vs 16.6 months), prostate-specific antigen (PSA) progression (33.2 vs 7.4 months), chemotherapy (NR vs 38.9 months), and subsequent prostate cancer therapy (NR vs 21.6 months). The hazard ratios for those endpoints ranged from 0.30 for PSA progression to 0.70 for pain progression in favor of the abiraterone arm, with P <.0001. The time to symptomatic skeletal-related events was not reached in both arms.
In terms of toxicities, the abiraterone-containing regimen resulted in higher rates of grade 3/4 adverse events compared with the control arm including hypertension (20.3% vs 10.0%); hypokalemia (10.4% vs 1.3%); elevated alanine aminotransferase (5.5% vs 1.3%), and elevated aspartate aminotransferase (4.4% vs 1.5%).
“We need to be cautious when using abiraterone in men who have an increased risk for heart problems, such as those with diabetes,” said Fizazi.
STAMPEDE Trial Results
The STAMPEDE trial is the largest study of first-line abiraterone ever conducted in patients with locally advanced or metastatic prostate therapy. In all, 1917 patients were randomized 1:1 to receive either abiraterone at 1000 mg daily plus prednisone at 5 mg daily plus standard of care (SOC) versus SOC alone. SOC consisted of ADT for at least 2 years with radiotherapy required for participants with N0M0 disease and encouraged for those with stage N+M0.
Treatment duration depended on stage and intent to administer radiotherapy: patients not receiving radiotherapy or with M1 disease were eligible to continue treatment until radiological, clinical, or prostate-specific antigen (PSA) progression. Other patients continued therapy at least 2 years or until progression.
The median age of participants was 67 years (range, 39-85 years); 52% had prostate cancer that had spread, of whom 88% had disease that spread to the bone; and 95% were newly diagnosed.
At a median follow up of 40 months, 184 deaths had occurred in the abiraterone group and 262 deaths in the standard therapy arm. The median adjusted HR for the median OS was 0.63 (95% CI, 0.52-0.76; P
= .0000012). Abiraterone-containing therapy also markedly improved skeletal-related outcomes with a 55% reduction in the time for such problems to develop (HR, O.45; 95% CI, 0.36-0.38).
Although most adverse events (AEs) were similar between the 2 groups, researchers reported that serious AEs occurred more frequently among participants who received abiraterone, with 41% of patients reporting grade 3/4 AEs compared with 29% in the standard therapy group.
As with the LATITUDE trial, the main AEs occurring more frequently with abiraterone were cardiovascular problems such as high blood pressure; there were also more liver problems. There were 2 treatment-related deaths in the abiraterone group and in the standard therapy group, researchers reported.
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- Fizaxi K, Tran N, Fein LE, et al; the LATITUDE investigators. LATITUDE: A phase 3 double-blind, randomized trial of androgen deprivation therapy (ADT) with abiraterone acetate (AA) plus prednisone (P) or placebos (PBOs) in newly diagnosed high-risk metastatic hormone-naïve prostate cancer (mHNPC) patients (pts). J Clin Oncol. 2017;35 (suppl; abstr LBA3).
- James ND, DeBono JS, Spears MR, et al. Adding abiraterone for men with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): Survival results from STAMPEDE (NCT00268476). J Clin Oncol. 2017;35 (suppl; abstr LBA5003).
- Sweeney C, Chen Y-H, Carducci MA, et al. Impact on OS with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer: an ECOG-led phase III randomized trial. J Clin Oncol. 2014;32 (5 suppl; abstr LBA2).
- James ND, Sydes, MR, Mason, MD, et al. Docetaxel and/or zoledronic acid for hormone-naïve prostate cancer: First overall survival results from STAMPEDE. J Clin Oncol. 2015;33 (suppl; abstr 5001).