Treatment with apalutamide (Erleada) resulted in a rapid and substantial decline in PSA, and greater magnitude of PSA decline correlated with improvement in several oncologic endpoints, results from the phase III SPARTAN study showed.
San Francisco-Treatment with apalutamide (Erleada) resulted in a rapid and substantial decline in PSA, and greater magnitude of PSA decline correlated with improvement in several oncologic endpoints, results from the phase III SPARTAN study showed.
In addition, analyses of PSA data collected in the study confirm that a shorter PSA doubling time (PSADT) is a poor prognostic factor for men with nonmetastatic castration-resistant prostate cancer (nmCRPC).
“These data demonstrate that the dramatic PSA declines observed with the use of apalutamide in nmCRPC are correlated with clinically meaningful endpoints such as time to metastasis and time to development of cancer-associated symptoms,” said first author Eric J. Small, MD, professor and chief of hematology and oncology and deputy director, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.
SPARTAN was a global study designed to evaluate the efficacy of apalutamide in men with nmCRPC who were at high risk for developing metastasis, defined by having a PSADT ≤10 months while on continuous androgen deprivation therapy (ADT). It randomized 1,207 patients 2:1 to continuous daily treatment with the oral next-generation androgen receptor inhibitor or matching placebo. All men received continuous ADT.
The apalutamide and control groups were well matched at baseline in their median values for PSA (7.78 and 7.96 ng/mL, respectively) and PSADT (4.40 and 4.50 months, respectively) and in other demographic and clinical characteristics.
Reviewing topline results, Dr. Small said that the primary endpoint analysis showed apalutamide significantly extended median metastasis-free survival (MFS) by 2 years compared with placebo (40.5 vs. 16.2 months). Benefit of apalutamide treatment was also seen in all secondary endpoint analyses, including time to symptomatic progression, and in the exploratory endpoint analysis of progression-free survival on second therapy initiated after metastasis (PFS2).
“I applaud the FDA for recognizing MFS as an important endpoint. In addition to a 2-year improvement in MFS, development of symptomatic progression is a very real event for patients, and apalutamide treatment was associated with a highly significant reduction in its risk,” said Dr. Small.
Blood samples for measuring PSA were collected at baseline and then every 4 weeks during the first 6 months of the study, every 8 weeks from months 7 through 13, and every 16 weeks thereafter. The assays were performed at a central laboratory.
The analyses of PSA data from the placebo arm showed that baseline PSADT predicted risks of metastasis or death, symptomatic progression, and PFS2.
Next: Time to PSA progression improvedTime to PSA progression improved
Comparisons between the placebo and apalutamide treatment arms showed time to PSA progression, which was defined as the time from randomization to PSA progression according to Prostate Cancer Working Group 2 criteria, was also significantly improved with apalutamide treatment, with a 94% reduction in risk of PSA progression; p<.0001).
At 12 weeks after randomization, median PSA decreased by 90% in the apalutamide group and increased by 40% in the placebo group. A ≥90% maximum decline in PSA from baseline at any time on study was observed in 66% of apalutamide-treated patients and 1% of controls.
Statistically significant differences favoring apalutamide were also achieved in analyses of the percentage of patients with a PSA decline ≥50%; 93% of men treated with apalutamide compared with just 2% of patients treated with placebo achieved a PSA response (p<.0001).
“Perhaps even more impressively, PSA fell to <0.2 ng/mL in a full 40% of apalutamide-treated patients and to ≤0.02 ng/mL in 13% of the apalutamide-treated men,” Dr. Small reported.
In the apalutamide group, median time to PSA decline ≥50% was <1 month, median nadir PSA was 0.36 ng/mL, and median time to nadir PSA was 6.4 months.
Analyses of associations between magnitude of the PSA response to apalutamide and various clinical endpoints showed that a greater magnitude of PSA decline was associated with greater improvement in MFS, time to symptomatic progression, and PFS2. For example, compared to men with a PSA decline <50%, men with a PSA decline from 50% to 90% had a 39% reduction in risk of developing metastases or death; patients with ≥90% decline in PSA had a 70% reduction in risk of developing metastases or death, and patients whose PSA fell to ≤0.02 ng/mL had a 95% reduction in risk of developing metastases or death. This pattern was also observed for symptomatic progression and PFS2.
Dr. Small has served as a consultant for and received honoraria from Janssen. Several of his co-authors have an investment interest in Johnson & Johnson and are employees of Janssen, and several co-authors have a disclosure related to Janssen and other pharmaceutical companies.