In the primary analysis at 378 events, median metastasis-free survival (MFS) was 40.5 months in the apalutamide group compared with 16.2 months in the placebo group (HR for metastasis or death 0.28, 95% CI 0.23-0.35). Time to symptomatic progression was significantly longer with apalutamide than with placebo (HR 0.45, 95%CI 0.32-0.63). Results from the SPARTAN trial demonstrated that apalutamide decreased the risk of metastasis or death by 72% and prolonged the median MFS by more than two years in men with high-risk nmCRPC. Furthermore, the MFS benefit was supported by consistent improvement across all evaluable endpoints: time to metastasis, PFS, time to symptomatic progression, time to PSA progression, and PSA decline. At 2018 ASCO annual meeting, Dr. Small and colleagues presented results of their post-hoc analysis of SPARTAN, assessing predictors of clinical endpoints among men with nmCRPC.
Key inclusion criteria for men enrolling in SPARTAN included:
- Histologically confirmed adenocarcinoma of the prostate, castration-resistant
- High risk of developing metastasis: PSA doubling time of 10 months or less during continuous ADT
- Negative bone scan and CT of the pelvis, abdomen, chest, and head
Among the 1207 patients included in SPARTAN (n=806 apalutamide; n=401 placebo), a relationship between shorter PSADT and faster time to metastasis or death was observed in the placebo arm:
The following covariates were independent predictors of longer MFS for the combined arms analysis:
- Apalutamide treatment: HR 0.26 (95%CI 0.21-0.32)
- PSADT > 6 months: HR 0.65 (95%CI 0.51-0.84)
- N0 disease: HR 0.68 (95%CI 0.52-0.89)
- Gleason score at diagnosis ≤ 7: HR 0.75 (95%CI 0.61-0.92)
- Baseline PSA ≤ 7.8 ng/mL: HR 0.59 (95%CI 0.47-0.73)
Even when adjusting for clinical predictors of MFS, apalutamide maintained a 74% risk of reduction for MFS, consistent with a similar magnitude of risk reduction as noted in the primary analysis (72% risk reduction). This study also highlights several other clinical predictors of metastasis, including PSADT, N0 disease, Gleason score, and baseline PSA.
Clinical trial information: NCT01946204
Presented By: Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
Co-Authors: Fred Saad, Dana E. Rathkopf, Boris A. Hadaschik, Simon Chowdhury, Margaret K. Yu, Angela Lopez-Gitlitz, Oliver Brendan Rooney, Youyi Shu, Mohamed Darif, Matthew Raymond Smith; Centre Hospitalier de l’Université de Montréal/CRCHUM, University of Montréal, Montréal, QC, Canada; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; University of Duisburg-Essen, Essen, Germany; Guy's, King's and St Thomas' Hospitals, London, United Kingdom; Janssen Research & Development, Los Angeles, CA; Janssen Research & Development, High Wycombe, United Kingdom; Janssen Research & Development, Collegeville, PA; Janssen Research & Development, San Diego, CA; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
1. Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.