Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial

Abstract

Purpose: Docetaxel and abiraterone acetate plus prednisone or prednisolone (AAP) both improve survival when commenced alongside standard of care (SOC) androgen deprivation therapy in locally advanced or metastatic hormone-sensitive prostate cancer. Thus, patient-reported quality of life (QOL) data may guide treatment choices.

Methods: A group of patients within the STAMPEDE trial were contemporaneously enrolled with the possibility of being randomly allocated to receive either docetaxel + SOC or AAP + SOC. A mixed-model assessed QOL in those who had completed at least one QLQ-C30 + PR25 questionnaire. The primary outcome measure was difference in global-QOL (QLQ-C30 Q29&30) between patients allocated to docetaxel + SOC or AAP + SOC over the 2 years after random assignment, with a predefined criterion for clinically meaningful difference of > 4.0 points. Secondary outcome measures included longitudinal comparison of functional domains, pain, and fatigue, plus global-QOL at defined timepoints.

Results: Five hundred fifteen patients (173 docetaxel + SOC and 342 AAP + SOC) were included. Baseline characteristics, proportion of missing data, and mean baseline global-QOL scores (docetaxel + SOC 77.8 and AAP + SOC 78.0) were similar. Over the 2 years following random assignment, the mean modeled global-QOL score was +3.9 points (95% CI, +0.5 to +7.2; P = .022) higher in patients allocated to AAP + SOC. Global-QOL was higher for patients allocated to AAP + SOC over the first year (+5.7 points, 95% CI, +3.0 to +8.5; P < .001), particularly at 12 (+7.0 points, 95% CI, +3.0 to +11.0; P = .001) and 24 weeks (+8.3 points, 95% CI, +4.0 to +12.6; P < .001).

Conclusion: Patient-reported QOL was superior for patients allocated to receive AAP + SOC, compared with docetaxel + SOC over a 2-year period, narrowly missing the predefined value for clinical significance. Patients receiving AAP + SOC reported clinically meaningful higher global-QOL scores throughout the first year following random assignment.

Trial registration: ClinicalTrials.gov NCT00268476.

Conflict of interest statement

Alicia K. MorgansHonoraria: Genentech, Janssen, Sanofi, AstraZeneca, Astellas Scientific and Medical Affairs Inc, Astellas Pharma, Janssen Oncology, Bayer, Janssen, Clovis Oncology, Myovant Sciences, Advanced Accelerator Applications, Exelixis, Pfizer, MerckConsulting or Advisory Role: AstraZeneca, Sanofi, Bayer, Astellas Pharma, Janssen, Advanced Accelerator Applications, Myovant Sciences, Blue Earth Diagnostics, Myovant Sciences, Exelixis, Novartis, Myriad Genetics, Lantheus Medical Imaging, MerckResearch Funding: Bayer, Seattle Genetics/Astellas, Genentech, AstraZeneca, Astellas Scientific and Medical Affairs Inc, Dendreon, Sanofi, Myovant SciencesTravel, Accommodations, Expenses: Sanofi Noel W. ClarkeHonoraria: Janssen-Cilag, Astellas Pharma, Sanofi, Bayer, AstraZeneca, Ferring, IpsenConsulting or Advisory Role: Astellas Pharma, Janssen-Cilag, Ferring, Bayer, SanofiSpeakers' Bureau: Janssen-Cilag, Astellas PharmaResearch Funding: AstrazenecaTravel, Accommodations, Expenses: Janssen-Cilag, Astellas Pharma, Sanofi, Bayer, AstraZeneca, Ferring, Ipsen Gerhardt AttardHonoraria: Astellas Pharma, Janssen (I)Consulting or Advisory Role: Janssen-Cilag, Veridex, Ventana Medical Systems, Astellas Pharma, Medivation, Novartis, Millennium, Abbott Laboratories, ESSA, Bayer, Pfizer, AstraZeneca, FerringSpeakers' Bureau: Janssen, Astellas Pharma, Takeda, Sanofi, Ventana Medical Systems, Ipsen, AstraZeneca, FerringResearch Funding: Janssen, Arno Therapeutics, Innocrin PharmaPatents, Royalties, Other Intellectual Property: I am on The ICR rewards to inventors list of abiraterone acetateTravel, Accommodations, Expenses: Astellas Pharma, Medivation, Ventana Medical Systems, Abbott Laboratories, Bayer, ESSA, Janssen (I), Astellas Pharma (I), Pfizer (I), FerringOther Relationship: Institute of Cancer Research David P. DearnaleyPatents, Royalties, Other Intellectual Property: Abiraterone acetate was developed at The Institute of Cancer Research, which therefore has a commercial interest in the development of this agent. Professor Dearnaley is on the Institute’s Rewards to Inventors list for abiraterone acetate, patent issued EP1933709B1 (location and stabilization device)Travel, Accommodations, Expenses: Janssen Oncology Christopher C. ParkerHonoraria: Bayer, JanssenConsulting or Advisory Role: Clarity Pharmaceuticals, Myovant Sciences, ITM Oncologics Silke GillessenConsulting or Advisory Role: Astellas Pharma (Inst), Janssen (Inst), Bayer (Inst), Orion Pharma GmbH, Tolero Pharmaceuticals (Inst), MSD Oncology (Inst), Roche (Inst), Amgen, Pfizer (Inst), BMS (Inst), Telix Pharma (Inst), MSD Oncology, AAA HealthCare (Inst), Orion Corporation (Inst), Amgen (Inst)Patents, Royalties, Other Intellectual Property: Method for biomarker (WO 3752009138392 A1)Travel, Accommodations, Expenses: ProteoMedixOther Relationship: ProteoMedix, Aranda Pharma (Inst), Menarini Silicon Biosystems (Inst) Christopher D. BrawleyResearch Funding: Astellas Pharma, Clovis Oncology, Janssen, Sanofi/Aventis, Pfizer, Novartis, Jacob S. TanguayConsulting or Advisory Role: AstraZeneca, Astellas Pharma, BayerTravel, Accommodations, Expenses: Janssen, Roche, Bayer Robert J. JonesHonoraria: Astellas Pharma, Janssen, AstraZeneca, MSD Oncology, Bristol Myers Squibb, Pfizer, Novartis, Ipsen, Seattle Genetics, Sanofi, Bayer, Roche/Genentech, EUSA Pharma, Pharmacyclics, Clovis OncologyResearch Funding: Roche, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Exelixis, Clovis Oncology, BayerTravel, Accommodations, Expenses: Ipsen, Bayer, Janssen, Astellas Pharma, MSD John WagstaffHonoraria: Bristol Myers Squibb, Roche, Pierre Fabre, Novartis, GlaxoSmithKline UK Ltd., PfizerConsulting or Advisory Role: Bristol Myers Squibb, Roche, Pfizer, Novartis, Pierre FabreSpeakers' Bureau: Bristol Myers Squibb Sarah RudmanHonoraria: Bristol Myers Squibb Foundation, EUSA Pharma, Ipsen, PfizerConsulting or Advisory Role: Ipsen, Pfizer, EUSA Pharma Joe M. O'SullivanConsulting or Advisory Role: Bayer, Janssen, Astellas Pharma, Sanofi, NovartisSpeakers' Bureau: Bayer, Janssen, NovartisResearch Funding: Bayer Alison BirtleHonoraria: Janssen-CilagConsulting or Advisory Role: Roche, Astellas Medivation, Janssen Oncology, AstraZeneca, Sanofi, Bayer Schering Pharma, Bristol Myers Squib, Merck Serono, PfizerSpeakers' Bureau: Bayer, Janssen Oncology, PfizerResearch Funding: Genzyme Andrew ProtheroeEmployment: Genesis Cancer CareHonoraria: Astellas Pharma, MSD Oncology, Ipsen, Astellas Pharma, Merck Serono, Eisai, MerckTravel, Accommodations, Expenses: Bayer, EUSA Pharma Emma GrayEmployment: Genesis Cancer CareHonoraria: Astellas Pharma, MSD Oncology, Ipsen, Astellas Pharma, Merck Serono, Eisai, MerckTravel, Accommodations, Expenses: Bayer, EUSA Pharma Neil McPhailConsulting or Advisory Role: Eisai, GlaxoSmithKline, IpsenTravel, Accommodations, Expenses: Ipsen Zaf I. MalikConsulting or Advisory Role: Sanofi/Aventis Salil VengalilHonoraria: Bristol Myers Squibb, PfizerConsulting or Advisory Role: Merck/PfizerTravel, Accommodations, Expenses: Ipsen Peter HoskinResearch Funding: Varian Medical Systems, Astellas Pharma, Bayer, Roche, Pfizer, Elekta Matthew R. SydesHonoraria: Lilly, Sanofi, JanssenResearch Funding: Astellas Pharma, Janssen-Cilag, Pfizer, Novartis, Sanofi, Clovis Oncology Simon ChowdhuryHonoraria: Clovis Oncology, NovartisConsulting or Advisory Role: Clovis Oncology, Astellas Pharma, Bayer, Pfizer, Janssen-Cilag, BeiGene, NovartisSpeakers' Bureau: Pfizer, Janssen-CilagResearch Funding: Sanofi/Aventis Mahesh K. B. ParmarResearch Funding: AstraZeneca, Astellas Pharma, Janssen, Clovis Oncology Nicholas D. JamesHonoraria: Sanofi, Bayer, Janssen, Astellas PharmaConsulting or Advisory Role: Sanofi, Bayer, Astellas Pharma, Janssen, Clovis Oncology, EUSA pharma, pfizerSpeakers' Bureau: Pierre Fabre, Ferring, Sanofi, Astellas Pharma, Janssen Oncology, MerckResearch Funding: Janssen, Astellas Pharma, Pfizer, Sanofi, Novartis, AstraZenecaTravel, Accommodations, Expenses: Sanofi, Janssen Ruth E. LangleyConsulting or Advisory Role: Bayer Schering PharmaResearch Funding: Bayer Schering PharmaNo other potential conflicts of interest were reported.

Figures

Fig 1

CONSORT diagram. AAP, abiraterone acetate plus prednisolone or prednisone; ADT, androgen deprivation therapy; M1, Metastatic prostate cancer; QOL, quality of life; RT, radiotherapy; SOC, standard of care; ZA, zoledronic acid.

Fig 2

Longitudinal analysis using a mixed-model approach of global-QOL scores. The red line shows global-QOL score for patients treated with AAP + SOC, whereas the blue line shows global-QOL score for patients treated with docetaxel + SOC over the 2 years following random assignment. The red and blue shaded areas show the 95% CI around each line. The black line shows global-QOL for patients receiving SOC alone. Higher scores indicate better QOL. The difference is calculated by subtracting the docetaxel + SOC score from the AAP + SOC score; a positive difference represents a higher QOLfor patients treated with AAP + SOC and negative difference represents a higher QOL for patients receiving docetaxel + SOC. All scores are corrected as per QLQ-C30 guidelines to range from 0 to 100. AAP, abiraterone acetate plus prednisone or prednisolone; QOL, quality of life; SOC, standard of care.

Fig 3

Longitudinal analysis showing QOL score for each functional domain over 2 years, separating scores for patients treated with docetaxel + SOC versus AAP + SOC. Higher scores indicate better quality of life. All scores are corrected as per QLQ-C30 guidelines to range from 0 to 100. Thedifference over2years is calculated by subtracting the docetaxel + SOC score from the AAP + SOC score; positive scores represent a higher QOL for patients treated with AAP + SOC and negative scores indicate a higher QOL for patients treated with docetaxel + SOC: (A) physical functioning domain, (B) social functioning domain, (C) role functioning domain, (D) cognitive functioning domain, and (E) emotional functioning domain. AAP, abiraterone acetate plus prednisone or prednisolone; QOL, quality of life; SOC, standard of care.

Fig 4

Longitudinal analysis showing QOL score for pain and fatigue symptoms over 2 years, separating scores for patients treated with docetaxel + SOC versus AAP + SOC. The difference over 2 years is calculated by subtracting the docetaxel + SOC score from the AAP + SOC score; a positive difference represents a higher symptom score for patients treated with AAP + SOC and a negative difference indicates a higher symptom score for patients receiving docetaxel + SOC. Higher scores indicate worse symptoms and quality of life. All scores are corrected as per QLQ-C30 guidelines to range from 0 to 100: (A) pain symptoms and (B) fatigue symptoms. AAP, abiraterone acetate plus prednisone or prednisolone; QOL, quality of life; SOC, standard of care.