TY - JOUR
T1 - Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer
T2 - an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial
AU - Saad, Fred
AU - Cella, David
AU - Basch, Ethan
AU - Hadaschik, Boris A.
AU - Mainwaring, Paul N.
AU - Oudard, Stéphane
AU - Graff, Julie N.
AU - McQuarrie, Kelly
AU - Li, Susan
AU - Hudgens, Stacie
AU - Lawson, Joe
AU - Lopez-Gitlitz, Angela
AU - Yu, Margaret K.
AU - Smith, Matthew R.
AU - Small, Eric J.
N1 - Funding Information:
FS reports grants, personal fees, and non-financial support from Janssen, Astellas, Sanofi, and Bayer. DC is a consultant to AbbVie, Astellas, Bayer, Bristol-Myers Squibb, Daiichi Sankyo Inc, Evidera, GlaxoSmithKline, Helsinn, Ipsen, Janssen Research & Development, and Novartis, and is the president of FACIT.org . BAH reports grants from German Cancer Aid, German Research Foundation, and Profound Medical; grants, personal fees, and non-financial support from Janssen; personal fees and non-financial support from Astellas and Bayer; and grants and personal fees from Uromed. PNM reports personal fees from XING Technologies P/L, Ipsen, Janssen, Novartis, Pfizer, and Roche; grants and personal fees from Merck; and has a patent pending with XING Technologies P/L. SO reports personal fees from Janssen, Sanofi, Astellas, Bayer, and Merck. JNG reports grants and personal fees from Janssen, Sanofi, and Astellas; personal fees from Bayer and Dendreon; and grants from Merck and Bristol-Myers Squibb. SH reports consulting fees from Janssen. MRS reports grants and personal fees from Janssen; and personal fees from Astellas and Bayer. KM, SL, JL, AL-G, and MKY are employed by Janssen Research & Development, and hold stock in Johnson & Johnson. EB and EJS declare no competing interests.
Funding Information:
This study was funded by Janssen Research & Development. Editorial assistance was provided by Ann P Tighe, PhD, of PAREXEL (Hackensack, NJ, USA), with funding from Janssen Global Services LLC (Raritan, NJ, USA).
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/10
Y1 - 2018/10
N2 - Background: In the SPARTAN trial, addition of apalutamide to androgen deprivation therapy, as compared with placebo plus androgen deprivation therapy, significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer who were at high risk for development of metastases. We aimed to investigate the effects of apalutamide versus placebo added to androgen deprivation therapy on health-related quality of life (HRQOL). Methods: SPARTAN is a multicentre, international, randomised, phase 3 trial. Participants were aged 18 years or older, with non-metastatic castration-resistant prostate cancer, a prostate-specific antigen doubling time of 10 months or less, and a prostate-specific antigen concentration of 2 ng/mL or more in serum. Patients were randomly assigned (2:1) to 240 mg oral apalutamide per day plus androgen deprivation therapy, or matched oral placebo plus androgen deprivation therapy, using an interactive voice randomisation system. Permuted block randomisation was used according to the three baseline stratification factors: prostate-specific antigen doubling time (>6 months vs ≤6 months), use of bone-sparing drugs (yes vs no), and presence of local-regional nodal disease (N0 vs N1). Each treatment cycle was 28 days. The primary endpoint was metastasis-free survival. The trial was unblinded in July, 2017. In this prespecified exploratory analysis we assessed HRQOL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaires, which we collected at baseline, day 1 of cycle 1 (before dose), day 1 of treatment cycles 1–6, day 1 of every two cycles from cycles 7 to 13, and day 1 of every four cycles thereafter. This study is registered with ClinicalTrials.gov, number NCT01946204. Findings: Between Oct 14, 2013, and Dec 15, 2016, we randomly assigned 1207 patients to receive apalutamide (n=806) or placebo (n=401). The clinical cutoff date, as for the primary analysis, was May 19, 2017. Median follow-up for overall survival was 20·3 months (IQR 14·8–26·6). FACT-P total and subscale scores were associated with a preservation of HRQOL from baseline to cycle 29 in the apalutamide group; there were similar results for EQ-5D-3L. At baseline, the mean for FACT-P total score in both the apalutamide and placebo groups were consistent with the FACT-P general population norm for US adult men. Group mean patient-reported outcome scores over time show that HRQOL was maintained from baseline after initiation of apalutamide treatment and was similar over time among patients receiving apalutamide versus placebo. Least-squares mean change from baseline shows that HRQOL deterioration was more apparent in the placebo group. Interpretation: In asymptomatic men with high-risk non-metastatic castration-resistant prostate cancer, HRQOL was maintained after initiation of apalutamide treatment. Considered with findings from SPARTAN, patients who received apalutamide had longer metastasis-free survival and longer time to symptomatic progression than did those who received placebo, while preserving HRQOL. Funding: Janssen Research & Development.
AB - Background: In the SPARTAN trial, addition of apalutamide to androgen deprivation therapy, as compared with placebo plus androgen deprivation therapy, significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer who were at high risk for development of metastases. We aimed to investigate the effects of apalutamide versus placebo added to androgen deprivation therapy on health-related quality of life (HRQOL). Methods: SPARTAN is a multicentre, international, randomised, phase 3 trial. Participants were aged 18 years or older, with non-metastatic castration-resistant prostate cancer, a prostate-specific antigen doubling time of 10 months or less, and a prostate-specific antigen concentration of 2 ng/mL or more in serum. Patients were randomly assigned (2:1) to 240 mg oral apalutamide per day plus androgen deprivation therapy, or matched oral placebo plus androgen deprivation therapy, using an interactive voice randomisation system. Permuted block randomisation was used according to the three baseline stratification factors: prostate-specific antigen doubling time (>6 months vs ≤6 months), use of bone-sparing drugs (yes vs no), and presence of local-regional nodal disease (N0 vs N1). Each treatment cycle was 28 days. The primary endpoint was metastasis-free survival. The trial was unblinded in July, 2017. In this prespecified exploratory analysis we assessed HRQOL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaires, which we collected at baseline, day 1 of cycle 1 (before dose), day 1 of treatment cycles 1–6, day 1 of every two cycles from cycles 7 to 13, and day 1 of every four cycles thereafter. This study is registered with ClinicalTrials.gov, number NCT01946204. Findings: Between Oct 14, 2013, and Dec 15, 2016, we randomly assigned 1207 patients to receive apalutamide (n=806) or placebo (n=401). The clinical cutoff date, as for the primary analysis, was May 19, 2017. Median follow-up for overall survival was 20·3 months (IQR 14·8–26·6). FACT-P total and subscale scores were associated with a preservation of HRQOL from baseline to cycle 29 in the apalutamide group; there were similar results for EQ-5D-3L. At baseline, the mean for FACT-P total score in both the apalutamide and placebo groups were consistent with the FACT-P general population norm for US adult men. Group mean patient-reported outcome scores over time show that HRQOL was maintained from baseline after initiation of apalutamide treatment and was similar over time among patients receiving apalutamide versus placebo. Least-squares mean change from baseline shows that HRQOL deterioration was more apparent in the placebo group. Interpretation: In asymptomatic men with high-risk non-metastatic castration-resistant prostate cancer, HRQOL was maintained after initiation of apalutamide treatment. Considered with findings from SPARTAN, patients who received apalutamide had longer metastasis-free survival and longer time to symptomatic progression than did those who received placebo, while preserving HRQOL. Funding: Janssen Research & Development.
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U2 - 10.1016/S1470-2045(18)30456-X
DO - 10.1016/S1470-2045(18)30456-X
M3 - Article
C2 - 30213449
AN - SCOPUS:85054773955
VL - 19
SP - 1404
EP - 1416
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 10
ER -