The positive results of STRIVE appear encouraging for the ongoing phase 3 PROSPER (Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer) trial, which is currently examining the effect of enzalutamide versus placebo on metastatic-free survival in patients with M0 CRPC.2
In terms of safety, both bicalutamide and enzalutamide were associated with similar rates of serious adverse events, grade ≥ 3 adverse events, and adverse events resulting in death.1
Both agents were linked with fatigue and hot flashes, which occurred more frequently with enzalutamide. Common adverse events, defined as those that occurred in 10% or more of patients, were reported more frequently in the enzalutamide group and included fatigue, back pain, hot flashes, hypertension, dizziness, and decreased appetite. Common adverse events that occurred more frequently with bicalutamide included constipation, diarrhea, anemia, and urinary tract infections.
“Patients have to weigh the risks and benefits in collaboration with their physician and decide if the benefit outweighs the risk,” said Dr Penson. “Personally I think it does…but each patient needs to make up his own mind with the help of his doctor.”
Sequencing of Agents an Important Question
One limitation of the study is that it did not address sequential therapy.
Before 2010, the chemotherapy agent docetaxel was the only therapy that had a proven survival benefit for CRPC. Since then, the development of multiple agents has improved the range of treatment options, but prospective data regarding the best order in which to use them are lacking.3
“STRIVE does show that in patients with M1 CRPC who were previously on androgen deprivation monotherapy, the common strategy of adding bicalutamide to the patients’ regimen and changing to enzalutamide when the bicalutamide fails is clearly inferior to just starting the enzalutamide upfront,” said Dr Penson.
“Clinicians need to seriously consider this going forward. At least in terms of progression-free survival, enzalutamide upfront is clearly a better way to go.”
Data from several trials that included patients across the CRPC spectrum suggested that earlier use of enzalutamide resulted in a greater benefit, with a longer time to disease progression in those treated with enzalutamide.
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For example, in the AFFIRM trial, patients with late-stage metastatic CRPC treated with enzalutamide had a median time to PSA progression of 8.3 months and patients with metastatic CRPC in the PREVAIL trial treated with enzalutamide prior to chemotherapy had a median time to PSA progression of 11.2 months.
“The big question in CRPC treatment in 2016 is: what is the best sequencing of agents in men with CRPC?” said Dr Penson. “I think it will take a number of years to determine this as we get longer follow-up in patients with CRPC treated with various agents and see which combination works best in which patients. There are a number of registry studies underway that will inform this discussion but it will be some time until we start to get an answer.”
Editor’s Note: The name of the STRIVE trial was originally incorrectly published. The error was corrected on February 16, 2016.
- Penson DF, Armstrong AJ, Concepcion R, et al. Enzalutamide versus bicalutamide in castration-resistant prostate cancer: the STRIVE trial [published online ahead of print January 25, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.64.9285.
- Hussain M, Fizazi K, Saad F, et al. PROSPER: a phase 3 study of enzalutamide in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) patients [abstract]. J Clin Oncol 32:5s, 2014 (suppl; abstr TPS5094).
- Lorente D, Mateo J, Perez-Lopez R, et al. Sequencing of agents in castration-resistant prostate cancer. Lancet Oncol. 2015;16(6):e279-e292.