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Benefit evident regardless of metastasis site, phase III analysis shows.
Chicago-Apalutamide (Erleada) treatment in men with nonmetastatic castrate-resistant prostate cancer (nmCRPC) significantly improves metastasis-free survival (MFS), and its benefit is evident regardless of the site of metastasis, according to a post-hoc analysis of data from the SPARTAN phase III clinical trial data presented at the 2018 American Society of Clinical Oncology annual meeting.
SPARTAN randomized 1,207 men with nmCRPC who were at high risk for developing metastasis (defined by having a PSA doubling time ≤10 months while on continuous androgen deprivation therapy) 2:1 to continuous daily treatment with apalutamide or matching placebo. Metastasis-free survival was analyzed as the primary endpoint, and the results showed that compared with placebo, apalutamide treatment reduced the relative risk of metastasis by 73% and delayed time to metastasis by a median of approximately 2 years (16.2 vs. 40.5 months).
The new analysis showed that treatment with apalutamide did not alter the pattern of metastasis. In both study arms, first metastasis occurred at a single site, with bone being the most common anatomic location followed by lymph nodes and viscera. Across the three anatomic sites, apalutamide consistently provided a statistically significant benefit for extending the time to metastasis.
“FDA approval of apalutamide for the treatment of nmCRPC was precedent setting because it was the first time the agency granted an approval to an oncology drug based on improvement in MFS,” lead author Matthew R. Smith, MD, professor of medicine at Harvard Medical School, Boston, told Urology Times. “In SPARTAN, MFS was a composite endpoint defined as the time from randomization to the first detection of distant metastasis on imaging or death. Distant metastasis accounted for most of the events, and we know that in terms of survival, the prognosis for men with metastatic CRPC varies depending on anatomic location of metastasis.
“The finding that apalutamide consistently prolonged time to metastasis regardless of its anatomic site reinforces the clinical benefit of treatment with this androgen receptor inhibitor,” he said.
Metastasis incidence 22% vs. 48%
In SPARTAN, the incidence of metastasis was 22% (175/806) in the apalutamide arm and 48% in the placebo arm (191/401). The incidence of bone, nodal, and visceral metastasis in the apalutamide arm was 57%, 30%, and 13%, respectively, and it was 52%, 40%, and 8%, respectively in the placebo arm. A single site was involved in the first metastatic event for 92% of apalutamide patients and 86% of men in the control group.
The analyses of time to metastasis showed that apalutamide reduced the relative risk by 73% overall (p<.0001) and by 69% for bone (p<.0001), 81% for nodal metastasis (p<.0001), and 49% for visceral metastasis (p=.043).
Dr. Smith is a consultant to Janssen Oncology and other companies that market treatments for prostate cancer.