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Despite prolonged progression-free duration, a 25% reduction in risk of death associated with anti-androgen agent apalutamide fell short of statistical significance in patients with non-metastatic, high-risk castration-resistant prostate cancer.
Despite prolonged progression-free duration, a 25% reduction in risk of death associated with nonsteroidal anti-androgen agent apalutamide (Erleada) fell short of statistical significance in patients with non-metastatic, high-risk castration-resistant prostate cancer (nmCRPC). This was shown in an updated interim analysis1 from the SPARTAN trial which was presented at the 2019 European Society of Medical Oncology (ESMO) meeting in Spain and in the Annals of Oncology.
Median overall survival (OS) has not been reached and definitive conclusions about apalutamide-associated survival benefits in nmCRPC patients depends on longer-term follow-up with more mature data, study authors reported. The study was funded by Janssen Research & Development.
“Because the difference in OS between groups did not cross the pre-specified O’Brien-Fleming boundary for statistical significance [of P= .0121], the final OS analysis will occur when 427 deaths are observed,” reported Eric J. Small, MD, of the UC San Francisco Helen Diller Family Comprehensive Cancer Center in California and coauthors.
A total of 1207 patients with nmCRPC were randomly assigned 2:1 to receive androgen deprivation therapy (ADT) plus either apalutamide (240 mg daily) or a placebo in the randomized, double-blind, placebo-controlled phase III trial. At median follow-up of 41 months, 4-year overall survival rates were 72.1% for patients receiving apalutamide vs 64.7% in the placebo arm (hazard ratio [HR] 0.75; 95% CI: 0.59-0.96; P= .0197). The statistically nonsignificant numeric survival benefit associated with apalutamide was “consistent” across all pre-specified subgroups analyzed.
“The [numerical] OS difference favoring apalutamide was observed despite a crossover of 19% of patients from placebo to apalutamide, and a higher use of subsequent life-prolonging therapy in the placebo group (69% versus 40%),” the study authors wrote.
Twenty-eight percent of apalutamide group patients and 37% of patients in the placebo group experienced disease progression during second-line therapy. Apalutamide was associated with an 11.8-month longer time to second disease progression (PFS2, an exploratory endpoint) than placebo (55.6 vs 43.8 months; HR 0.55; 95% CI: 0.45-0.68; P< .0001).
Fifty-three percent of patients receiving apalutamide experienced grade 3 or 4 adverse events, and 33.5% experienced serious adverse events, with 13.6% of patients discontinuing treatment because of toxicities. The most frequent grade 3 or 4 adverse event was hypertension (16%). Other common adverse reactions included fatigue, arthralgia, rash, decreased appetite, fall, weight loss, hot flush, diarrhea, and fracture. Grade 3 or 4 anemia was reported for 70% of patients on apalutamide; 47% experienced leukopenia, and 41% experienced lymphopenia.
1. E J Small, F Saad, S Chowdhury, S Oudard, B A Hadaschik, J N Graff, D Olmos, P N Mainwaring, J Y Lee, H Uemura, P De Porre, A A Smith, K Zhang, A Lopez-Gitlitz, M R Smith, Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer, Annals of Oncology, https://doi.org/10.1093/annonc/mdz397