Final SPARTAN analysis highlights treatment potential of apalutamide for nmCRPC
In the prespecified, event-driven final analysis of the phase III SPARTAN* trial, adding the androgen receptor inhibitor (ARi) apalutamide to androgen deprivation therapy (ADT) significantly improved overall survival (OS) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC).
One of the principal goals of nmCRPC therapy is the extension of OS. [J Clin Oncol 2005;23:2918-2925, Lancet Oncol 2018;19:1404-1416] In the interim analyses of SPARTAN, OS consistently favoured apalutamide over placebo; however, data were immature at the time. [N Engl J Med 2018;378:1408-1418; Ann Oncol 2019;30:1813-1820]
In this final analysis of SPARTAN, OS was markedly longer with apalutamide vs placebo and achieved the prespecified statistical significance (median, 73.9 vs 59.9 months, hazard ratio [HR], 0.78; p=0.016). This translates to a 22-percent reduction in the hazard of death and >1-year increase in median OS with apalutamide. [Eur Urol 2020;doi:10.1016/j.eururo.2020.08.011]
“The survival benefit of apalutamide added to ongoing ADT was observed despite the crossover of 19 percent of placebo-treated patients to apalutamide, and the frequent use of subsequent life-prolonging therapy … in the placebo arm (84 percent),” noted the researchers. Forty-six percent of apalutamide recipients had subsequent life-prolonging therapy. The OS extension with apalutamide thus conferred an impactful benefit in this setting, they added.
The OS findings were mirrored in two sensitivity analyses – naïve censoring and IPCW** – which accounted for placebo recipients who crossed over to apalutamide. Both analyses revealed an OS increase by 21.1 months with apalutamide vs placebo (median, 73.9 vs 52.8 months; HR, 0.69 for both). “These analyses delineated the impact of crossover treatment in the placebo arm. The treatment effect of apalutamide on survival was generally observed in the subpopulations evaluated, with exceptions in those with small numbers of patients,” they explained.
The hazard of initiating cytotoxic chemotherapy (CT) also dropped by 37 percent with apalutamide vs placebo (HR, 0.63; p=0.0002).
Safety consistent with previous reports
Median treatment duration was nearly three times longer with apalutamide vs placebo (32.9 vs 11.5 months). In the crossover arm, median treatment duration went beyond 2 years (26.1 months), which was about twice the durations reported in crossover arms of other nmCRPC studies ie, the PROSPER and ARAMIS trials (14.5 and 11.0 months, respectively). [N Engl J Med 2020;382:2197-2206; J Clin Oncol 2020;38(suppl 15):5514]
Despite the long treatment durations associated with apalutamide use, the overall incidence of any adverse event (AE) was similar across all arms (97, 94, and 89 percent of participants in the apalutamide, placebo, and crossover arms, respectively). Discontinuation rates due to AEs in the above-noted respective groups were also low at 15, 7, and 11 percent.
The overall safety results were consistent with those previously reported, noted the researchers.
A major advance in treatment
Participants (n=1,207) received either apalutamide 240 mg daily or placebo at a 2:1 ratio on top of ADT. Seventy-six placebo recipients crossed over to apalutamide after the primary endpoint of metastasis-free survival (MFS) was met.
The primary results of SPARTAN propelled the FDA approval of apalutamide for nmCRPC in 2018. [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-apalutamide-non-metastatic-castration-resistant-prostate-cancer, accessed October 30, 2020] “[Taking the primary and the current results together,] all endpoints*** … favoured treatment of patients with nmCRPC using apalutamide … while preserving health-related quality of life,” said the researchers.
Moreover, the findings support data from studies evaluating other ARis for nmCRPC, [N Engl J Med 2018;378:2465-2474; N Engl J Med 2019;380:1235-1246] thus reinforcing the therapeutic potential of ARis in this setting, and representing a major advance in nmCRPC treatment, they added.
“Without further treatment, patients with nmCRPC invariably progress to metastatic disease, with significant morbidity and mortality … [The] findings demonstrate the value of apalutamide as a treatment option for nmCRPC,” they said.