Adding apalutamide prior to metastases may benefit men with prostate cancer who are no longer responding to androgen deprivation therapy, according to new phase III study findings.
Adding apalutamide prior to metastases may benefit men with prostate cancer who are no longer responding to androgen deprivation therapy (ADT), according to the latest findings from the phase III placebo-controlled SPARTAN trial.
The data, which were presented at a presscast in advance of the Genitourinary Cancers Symposium in San Francisco, suggest that apalutamide is an effective treatment for men with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk for developing metastatic disease.
Men who received apalutamide, which is an orally administered next-generation androgen receptor inhibitor, had a 72% lower risk of metastasis or death than those men who received placebo (HR=0.28; 95% CI: 0.23-0.35; p<.0001). The study showed that the median metastasis-free survival was 40.5 months compared to 16.2 months for the placebo group. Study investigator Fred Saad, MD, of Centre Hospitalier de l’UniversitÃ© de MontrÃ©al, Montreal, said men who have nmCRPC and do not have visible metastasis unfortunately have no effective treatment options even though they are at high risk of developing metastases.
“As urologists, it has been extremely frustrating having nothing to offer patients except to image them until we confirm the presence of metastases-obviously, a very stressful situation for patients, who do not understand why we would wait so long to intervene. Hopefully, the findings from this study will rapidly lead to a treatment option for high-risk patients,” Dr. Saad told Urology Times. He worked on the study with lead author Eric J. Small, MD, of the University of California, San Francisco, and colleagues.
The SPARTAN Study was conducted at 332 institutions worldwide and enrolled 1,207 men. All the men had nmCRPC and were at high risk of metastasis based on a PSA doubling time of 10 months or less. The men were randomly assigned to receive apalutamide, 240 mg, or placebo taken orally once per day, added to ongoing ADT. At the time of development of metastases, patients were treated with standard second therapies and had an option to receive on-study abiraterone acetate (ZYTIGA) and prednisone. The median PSA doubling time at study entry was approximately 4.5 months in both the apalutamide and placebo groups.
At this interim analysis for overall survival (OS), the authors reported a trend favoring improved OS for men receiving apalutamide versus placebo. However, the difference was not statistically significant. Following the analysis of metastasis-free survival, study treatment was unblinded in July 2017 and all patients were offered open-label apalutamide. The current analysis revealed that secondary endpoints (time to metastasis, progression-free survival, and time to symptomatic progression) were all significantly improved. Apalutamide was well tolerated, with 10.7% of men discontinuing treatment due to adverse events compared with 6.3% of men receiving placebo. Quality of life scores were maintained in those men receiving apalutamide added to ADT.
The authors next plan to identify the subset of patients who benefited the most from apalutamide and analyze molecular and circulating blood markers. They also plan to look more closely at the patient-reported outcomes to better understand the patients’ perspective.
“Not all patients are at the same level of risk of early metastases. So, we will have to have some framework for establishing when and in whom this treatment will be most appropriate,” Dr. Saad explained.
Kelvin A. Moses, MD, PhD, of Vanderbilt University Medical Center, Nashville, TN, said the results are exciting and provide a new option for this patient population.
“Men in this setting with a rapidly rising PSA are typically managed with observation, potentially leading to increased anxiety. Apalutamide gives patients and their physicians an oral therapy option in addition to ADT to prolong metastasis-free survival, though there does not appear to be a significant difference in overall survival,” Dr. Moses told Urology Times.
Apalutamide appears to have a tolerable effect on quality of life. Dr. Moses said these new data will likely lead to the addition of apalutamide in the armamentarium of physicians who manage these complex patients. In addition, he said with further subset analyses it soon may be possible for urologists to offer a much more personalized approach to therapy.
Dr. Saad has received honoraria from and serves as a consultant/adviser to Janssen Oncology and several other pharmaceutical companies. His institution has also received research funding from Janssen Oncology several other pharmaceutical companies. For full disclosures, click here.
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