Apalutamide improves OS in nonmetastatic, castration-resistant prostate cancer
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BARCELONA, Spain — Apalutamide with ongoing androgen deprivation therapy improved OS compared with placebo among men with nonmetastatic, castration-resistant prostate cancer, according to updated results of the randomized phase 3 SPARTAN study presented at European Society for Medical Oncology Congress.
The results, while not statistically significant based on the target boundary, still support apalutamide (Erleada, Janssen Oncology) as a standard of care for this patient population, researchers noted.
“Apalutamide was associated with a 25% reduction in the risk for death compared with placebo,” Matthew R. Smith, MD, PhD, director of the genitourinary malignancies program at Massachusetts General Hospital Cancer Center, said during his presentation. “This OS benefit was observed despite [patients switching from placebo to apalutamide] and higher rates of subsequent life-prolonging therapy for [patients taking placebo].”
Previous results from the phase 3 SPARTAN study showed apalutamide with ongoing ADT significantly improved metastasis-free survival (HR = 0.28; 95% CI, 0.23-0.35), time to symptomatic progression, and PFS on second therapy compared with placebo with ongoing ADT. The results also suggested improved OS with apalutamide but the data were immature at that time.
Smith and colleagues presented results of a second interim analysis for OS after 65% of the 427 required events.
The researchers randomly assigned 1,207 men with nonmetastatic, castration-resistant prostate cancer and a PSA doubling time of at least 10 months to ongoing ADT with apalutamide dosed at 240 mg daily (n = 806) or placebo (n = 401).
Median follow-up was 41 months.
After 285 OS events, results showed apalutamide was associated with improved OS compared with placebo (HR = 0.75; 95% CI, 0.59-0.96). Four-year OS rates were 72.1% for men who received apalutamide and 64.7% for men who received placebo.
Although the OS benefit was determined to be 25%, the P value associated with it was .0197, which fell short of the boundary for statistical significance (P = .0121)
Results also showed benefit in PFS2 — an exploratory endpoint in the trial — with apalutamide (55.6 months vs. 43.8 months; HR = 0.55; 95% CI, 0.45-0.68).
Rates of discontinuation because of progressive disease were 34% in the apalutamide group and 74% in the placebo group. A higher percentage of patients assigned apalutamide discontinued due to adverse events (14% vs. 8%).
Treatment-related adverse events appeared consistent with previous analyses.
“These results further support apalutamide as a standard-of-care option for patients with high-risk, nonmetastatic castration-resistant prostate cancer,” Smith said. – by John DeRosier
Reference:
Smith MR, et al. Abstract 8430. Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.
Disclosures: Janssen funded this study. Smith reports consultant/advisory roles with Amgen, Bayer, Janssen and Pfizer, as well as research grants/funding from Bayer, Janssen and Gilead. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Karim Fizazi, MD, PhD
Until recently, there were no real options for patients with castration-resistant prostate cancer. In the last 2 years, however, we have seen data from three landmark phase 3 trials that clearly establish androgen receptor targeting is associated with improvement in metastasis-free survival, which was the primary endpoint.
Looking at the secondary endpoint of OS in this trial, researchers report that apalutamide decreased the risk for death by 25%. Although this is true, when you look at the HR of 0.75, the number is still a statistically nonsignificant difference with a P value of .02. The boundary for claiming victory on OS was a P value of .01. At the moment, we cannot say that apalutamide prolongs survival in this setting. However, we need to stay tuned because there are more data to come.
A meaningful difference in this study was the improvement of PFS2. The HR was 0.55, meaning a 45% difference in risk.
There are still unanswered questions from this trial. We still don’t know how active or inactive ADT is after apalutamide in the experimental arm. Indeed, many retrospective data strongly suggest that sequential use of next-generation androgen receptor targeting agents doesn’t really work.
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