Apalutamide Reduces Risk of Death in Patients With Nonmetastatic CRPC

Barcelona, Spain—Results from a second interim analysis for overall survival (OS) from the phase 3 SPARTAN study, presented at the ESMO 2019 Congress, show apalutamide is associated with a 25% reduction in the risk of death compared with placebo in patients with nonmetastatic castration-resistant prostate cancer (CRPC).

The phase 3 SPARTAN study evaluated the addition of apalutamide or placebo to androgen deprivation therapy in men with high-risk nonmetastatic CRPC. A total of 1207 patients were randomized in a 2:1 ratio to either apalutamide or placebo.  

“As previously reported, apalutamide significantly improved median metastases-free survival by more than 2 years and reduced the risk of metastases or death by 72%. Apalutamide also significantly improved time to symptomatic progression,” explained Matthew Smith, Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, during his presentation.

Because of this, the study was unblinded and apalutamide was offered to patients on placebo. A total of 76 patients who did no progress on placebo were crossed over to open-label apalutamide

“At the primary analysis for MFS, the survival data were immature, with only 104 of 427 events (24%) required for the prespecified final OS analysis,” Dr Smith added.

At 41 months median follow-up and 285 events, Dr Smith and colleagues conducted a second interim analysis for OS. At the time of the second interim analysis, apalutamide was associated with improved OS compared with placebo HR, 0.75; 95% CI, 0.59-0.96; P=0.0197). The 4-year OS rates for apalutamide and placebo were 72.1% and 64.7%, respectively.

At the second interim analysis, 68% of patients in the placebo group and 38% of patients in the apalutamide group received subsequent life-prolonging therapy.

The median treatment duration for apalutamide was 31.4 months compared to 11.5 months for placebo. Discontinuation rates due to progressive disease of adverse events (AEs) were 34% and 14%, respectively, in the apalutamide arm and 74% and 8%, respectively, in the placebo arm. Treatment-related AEs were similar to rates reported at the first interim analysis.

“In summary, apalutamide is associated with 25% reduction in risk of death compared to placebo; this OS benefit for apalutamide was observed despite crossover of placebo patients to apalutamide and higher rates of subsequent life-prolonging therapy than the placebo group,” said Dr Smith, adding that the OS improved was consistent across subgroups and the apalutamide safety profile remains unchanged with further follow-up.

“Collectively these results provide further support for apalutamide as a standard of care option for men with high-risk nonmetastatic CRPC,” Dr Smith concluded.—Janelle Bradley

Smith MR, Saad F, et al. Apalutamide (APA) and Overall Survival (OS) in Patients (pts) With Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): Updated Results From the Phase 3 SPARTAN Study. Presented at: ESMO 2019 Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract 843O.