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Bending the Curve Trial by Trial
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SPARTAN

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

Phase 3N = 1,207NCT01946204

Population
Men with nonmetastatic castration-resistant prostate cancer and PSA doubling time of 10 months or less
Design
Double-blind, placebo-controlled phase 3 trial, 2:1 randomization to apalutamide 240 mg per day or placebo, all continuing ADT. Eligibility: nonmetastatic castration-resistant prostate cancer by conventional imaging and PSA doubling time of 10 months or less. Primary end point metastasis-free survival (time from randomization to first detection of distant metastasis on imaging, or death).
Primary endpoint
MFS
Arms
  • Placebo plus ADT (control, n = 401): Placebo plus continued ADT
  • Apalutamide plus ADT (experimental, n = 806): Apalutamide 240 mg per day plus continued ADT
People
Smith MR, SPARTAN
MFSHR 0.28 (95% CI 0.23–0.35)Δ median MFS+24.3 monthsOSHR 0.78 (95% CI 0.64–0.96)Δ median OS+14 months
Show the numbers
Results reported for SPARTAN
EndpointAnalysisApalutamide plus ADTPlacebo plus ADTEffect
MFSRandomized men (analysis population not stated in the abstract)primarySmith 2018median 40.5 monthsmedian 16.2 monthsHR 0.28 (95% CI 0.23–0.35)P<0.001Planned primary analysis after 378 events. Hazard ratio for metastasis or death.
OSRandomized men (1207; 76 placebo patients, 19%, crossed over to apalutamide after unblinding)finalmedian follow-up 52 monthsSmith 2021median 73.9 monthsmedian 59.9 monthsHR 0.78 (95% CI 0.64–0.96)P=0.016Prespecified event-driven final analysis after 428 deaths, by group-sequential testing.
Results reported for SPARTAN
EndpointAnalysisApalutamide plus ADTPlacebo plus ADTEffect
MFSRandomized men (analysis population not stated in the abstract)primarySmith 2018median 40.5 monthsmedian 16.2 monthsHR 0.28 (95% CI 0.23–0.35)P<0.001Planned primary analysis after 378 events. Hazard ratio for metastasis or death.
OSRandomized men (1207; 76 placebo patients, 19%, crossed over to apalutamide after unblinding)finalmedian follow-up 52 monthsSmith 2021median 73.9 monthsmedian 59.9 monthsHR 0.78 (95% CI 0.64–0.96)P=0.016Prespecified event-driven final analysis after 428 deaths, by group-sequential testing.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
MFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
MFS0.280.23–0.35
OS0.780.64–0.96
Illustrative — modelled from reported values, not trial data. MFS, primary.
0%25%50%75%100%020406080100Months (modelled)
  • Placebo plus ADT (control)
  • Apalutamide plus ADT (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPlacebo plus ADTApalutamide plus ADT
0100.0%100.0%
2534.3%65.2%
5111.3%41.8%
763.9%27.2%
1011.3%17.8%
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%050100150Months (modelled)
  • Placebo plus ADT (control)
  • Apalutamide plus ADT (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPlacebo plus ADTApalutamide plus ADT
0100.0%100.0%
4658.7%65.0%
9234.5%42.2%
13920.0%27.2%
18511.8%17.6%
Primary publication: Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018;378(15):1408-1418. PubMedDOI

Appears in

Sources

  1. Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018;378(15):1408-1418.

    PubMedDOI

  2. Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021;79(1):150-158.

    PubMedDOI