Figure 1 – SPARTAN study design:
This study demonstrated that Apalutamide significantly prolonged metastasis-free survival, time to symptomatic progression, and second progression-free survival, without any decline in health-related quality of life.2 Another interesting finding is that SPARTAN patients who received apalutamide, compared to those who received placebo had a higher rate of falls (15.6% vs. 9.0%) and fractures (11.7% vs. 6.5%). In the presented study, the authors performed an analysis to identify independent clinical characteristics associated with falls and fractures in patients who were treated with apalutamide.
Out of the 1207 patients enrolled in this study, a total of 806 patients were randomized to receive apalutamide. The authors performed a univariate Cox proportional hazards model to assess the association of 47 baseline clinical characteristics with time to fall or time to fracture. Next, the authors performed a Cox proportional multivariable analysis with variables that produced a p-value of <0.1 in the univariable analysis, to determine independent factors associated with these outcomes (Table 1).
Table 1 – Candidate baseline and post-baseline covariates of time to fall and time to fracture that underwent analysis:
In the presented results, treatment-emergent falls and fractures were reported for 125 (16%) and 94 (12%) apalutamide-treated patients, respectively. Most falls and fractures were grade 1, or 2, non-disabling, and did not require hospitalization or surgical intervention. The median time to first fall among patients who experienced treatment-emergent fall was 9.2 months, and the median time to first fracture among patients who experienced treatment-emergent fracture was 10.3 months. On multivariable analysis with only baseline covariates, older age, poor ECOG performance status (PS), history of neuropathy, and pre-study alpha-blocker use were independently associated with time to falls (Table 2). The final multivariable model with baseline and postbaseline covariates showed that the baseline covariates of age, ECOG PS, history of neuropathy, and history of pre-study alpha-blocker use, and the postbaseline treatment-emergent adverse events of neuropathy, arthralgia, and weight decrease were independent predictors of time to fall (Table 3).
Table 2 – Independent baseline predictors of time to fall in the final multivariable model:
Table 3 - Independent baseline and postbaseline predictors of time to fall in the final multivariable model:
The final multivariable model with baseline covariates identified older age and lower serum albumin as independent baseline predictors of time to fracture (Table 4). The final multivariable model with baseline and postbaseline covariates identified baseline covariates of older age and lower serum albumin and postbaseline treatment-emergent adverse effects of fall prior to the day of fracture and developing neuropathy as independent predictors of time to fracture (Table 5).
Table 4 – Independent baseline predictors of time to fracture in the final multivariable model:
Table 5 – Independent baseline and postbaseline predictors of time to fracture in the final multivariable model:
In conclusion, initiating apalutamide in nmCRPC patients with ongoing ADT increased the risk of falls and fractures. The covariates found to be associated with increased risk of falls and fractures can help us identify at-risk candidates for preventive intervention, before and after initiation of apalutamide.
Presented by: YaoYao Guan Pollock, MD, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2019 ASCO Annual Meeting #ASCO19, May 31-June 4, 2019, Chicago, IL USA
- MR Smith et al. "Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer." New England Journal of Medicine. 2018. DOI: 10.1056/NEJMoa1715546.
- Saad et al. "Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial." Lancet Oncology. 2018. doi: 10.1016/S1470-2045(18)30456-X.