Final survival results from phase 3 SPARTAN trial

Featured video: Final survival results from SPARTAN, a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC).

In the phase 3 SPARTAN trial, the addition of apalutamide to androgen-deprivation therapy (ADT) improved median metastasis-free survival (MFS) and progression-free survival (PFS) in non-metastatic castration-resistant prostate cancer (nmCRPC), compared with placebo [1]. Now, overall survival data are mature, and this was also significantly improved in patients treated with apalutamide.

ADT is the mainstay of treatment for metastatic prostate cancer. ADT is also an important part of care for many men with non-metastatic prostate cancer. However, although ADT is initially effective, castration-resistant disease eventually develops in almost all men with prostate cancer.

The phase 3 SPARTAN trial evaluated the effect of adding the non-steroidal anti-androgen agent apalutamide to ADT in patients with nmCRPC. A total of 1,207 patients were 2:1 randomised to apalutamide (240 mg once daily) or placebo. At the primary endpoint analysis, apalutamide showed to significantly improve median MFS (40.5 months vs 16.2 months; HR 0.28; 95% CI 0.23-0.35; P<0.001), as well as median PFS (40.5 months vs 14.7 months; HR 0.29; 95% CI 0.24-0.36; P<0.001) compared with placebo [1]. Based on these primary study results, apalutamide was approved by the US FDA in February of 2018 for the treatment of men with nmCRPC.

After the primary efficacy endpoint of SPARTAN was met, the study was unblinded and eligible placebo patients crossed over to receive open-label apalutamide. In total, 76 patients in the placebo arm (19%) crossed over to apalutamide. After a median follow-up of 52 months and with 100% of the events required, the results of the secondary endpoint overall survival are mature. Apalutamide increased overall survival from 59.9 months to 73.9 months (HR 0.78; 95% CI 0.64-0.96; P=0.016) [2]. The improvement in overall survival was observed despite a high rate of subsequent active therapy, with 70% of placebo patients receiving life-prolonging therapy upon progression. Apalutamide also significantly delayed time to chemotherapy (HR 0.63; 95% CI 0.49-0.8; P=0.0002) as well as median time to PSA progression (40.5 months vs 3.7 months; HR 0.07; 95% CI 0.06-0.09; P<0.0001).

With substantially longer follow-up, the overall distribution of adverse events over time was stable and the safety profile of apalutamide was unchanged from the prior interim analysis.

1. 
   
   1. Smith MR, et al. N Engl J Med. 2018; 378: 1408-1418.
   2. Small EJ, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract 5516.

Posted on 17 September 202027 June 2024