New Orleans, LA—For patients with metastatic hormone-naïve prostate cancer, practice-changing results from the LATITUDE clinical trial showed that the use of abiraterone plus low-dose prednisone in addition to androgen-deprivation therapy (ADT) delayed disease progression by an average of 18 months, and reduced the risk for death by 38%, when compared with ADT alone.
The study was presented at the 2017 American Society of Clinical Oncology Annual Meeting, and later discussed by Lorinda A. Coombs, PhD candidate, MSN, RN, FNP-BC, AOCNP, Assistant Clinical Professor, University of California San Francisco School of Nursing, at the 12th Annual New Orleans Summer Cancer Meeting.
The current standard of care for metastatic hormone-naïve prostate cancer is docetaxel plus ADT. However, older patients with prostate cancer “often have comorbidities, and those comorbidities contribute to a poor performance status, which is exacerbated by the use of docetaxel,” Ms Coombs said.
She went on to say that the incidence of metastatic prostate cancer continues to rise in the United States. Some experts have hypothesized that changes in the screening guidelines regarding routine prostate-specific antigen testing have resulted in patients with prostate cancer being diagnosed later in the course of their disease.
“I don’t think we have enough evidence to know that for certain, but it definitely suggests that our screening methods should come under scrutiny,” Ms Coombs said.
Prostate cancer growth is fueled by testosterone, and ADT prevents testicles from making testosterone. However, despite ADT, the adrenal glands and prostate cancer cells continue to make small amounts of androgen. Abiraterone stops the production of testosterone by blocking an enzyme that converts other hormones to testosterone.
Increase in Overall Survival a “Home Run”
The double-blind, placebo-controlled phase 3 LATITUDE clinical trial enrolled 1199 men at 235 sites in 34 countries. Patients in the study were aged >18 years, with an Eastern Cooperative Oncology Group Performance Status score 0 to 2.
“Very functional patients were enrolled in this trial,” noted Ms Coombs. Patients were newly diagnosed (≤3 months) and had not previously received ADT.
All patients had at least 2 of 3 risk factors, including a Gleason score ≥8, ≥3 bony lesions, or measurable visceral metastases (spread to other organs in certain areas of the body, such as the liver).
“This was not subtle disease,” she added.
Patients were randomized 1:1 to ADT plus abiraterone (1000 mg daily) and prednisone (5 mg daily), or to ADT plus dual placebos. Co-primary end points were overall survival (OS) and radiographic progression-free survival.
After a median follow-up of 30.4 months, patients in the abiraterone group showed significant improvements in OS. Median OS in the placebo group was 34.7 months, and was not reached in the abiraterone group.
“That’s what you call a home run in terms of a clinical trial,” she said. These findings led to a unanimous agreement to unblind the study and allow for crossover.
“Patients who received abiraterone lived longer, and that is always the gold standard of any randomized controlled trial. You want to see a real-time benefit, not a subtle one,” said Ms Coombs.
Abiraterone also delayed cancer progression by approximately 18 months, and median progression-free survival was 33 months in the group that received the drug, compared with 14.8 months in the placebo group.
“But nothing in life or in cancer therapy is free,” she added. Ninety-three percent of patients in both arms experienced some sort of treatment-related adverse event, but grade 3 or 4 adverse events were more prevalent in the abiraterone group. Hypertension occurred in 37% of patients in the abiraterone group compared with 22% in the placebo group, and hypokalemia was observed in 20% and 4% of patients, respectively.
“In short, abiraterone plus prednisone increases OS, so we should be starting patients with metastatic hormone-naïve prostate cancer on this regimen. These significant results will influence practice,” asserted Ms Coombs.
However, it is important to monitor for grade ≥3 hypertension and hypokalemia in patients receiving this regimen.