TY - JOUR
T1 - Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD)
T2 - an analysis of a randomised, multicentre, open-label, phase 4 study
AU - Fizazi, Karim
AU - Kramer, Gero
AU - Eymard, Jean Christophe
AU - Sternberg, Cora N.
AU - de Bono, Johann
AU - Castellano, Daniel
AU - Tombal, Bertrand
AU - Wülfing, Christian
AU - Liontos, Michael
AU - Carles, Joan
AU - Iacovelli, Roberto
AU - Melichar, Bohuslav
AU - Sverrisdóttir, Ásgerður
AU - Theodore, Christine
AU - Feyerabend, Susan
AU - Helissey, Carole
AU - Oudard, Stéphane
AU - Facchini, Gaetano
AU - Poole, Elizabeth M.
AU - Ozatilgan, Ayse
AU - Geffriaud-Ricouard, Christine
AU - Bensfia, Samira
AU - de Wit, Ronald
N1 - Funding Information:
The funder of the study provided the study treatments, and collaborated with the authors on study design, data analysis, data interpretation, and writing of the report. The funder had no role in data collection. The manuscript was written with editorial support from medical writers, funded by the sponsor. The corresponding author had full access to all the data in the study and had the final responsibility for the decision to submit for publication.
Funding Information:
KF has received honoraria from and provided an advisory role for Astellas, AAA, Bayer, Essa, Janssen, Orion, CureVac, Clovis, Sanofi, and Endocyte. GK has received personal fees from Sanofi, Astellas, Takeda, Bayer, Janssen, Novartis, Ipsen, and AstraZeneca, and has received grants from Sanofi and Bayer. J-CE has received honoraria from and provided an advisory role for Astellas, Bristol-Myers Squibb, Ipsen, Janssen, Pfizer, and Sanofi Aventis, and has received travel and accommodation fees from Pfizer and Bristol-Myers Squibb. CNS has received honoraria from Janssen, AstraZeneca, Sanofi, and Astellas; consultancy fees from Sanofi, Bayer, and Pfizer; and institutional funding from Genentech–Roche, Bayer, Sanofi Genzyme, Janssen, Medivation, Merck Sharp and Dohme, and Exelixis. JdB has received honoraria from AstraZeneca, Sanofi, Astellas Pharma, Pfizer, Genentech–Roche, Janssen Oncology, Menarini Silicon Biosystems, Daiichi Sankyo, Sierra Oncology, and BioXcel Therapeutics, and provided an advisory role for AstraZeneca, Sanofi, Genentech–Roche, Astellas Pharma, Bayer, Pfizer, Merck Sharp and Dohme, Merck Serono, Boehringer Ingelheim, Sierra Oncology, Menarini Silicon Biosystems, Celgene, Taiho Pharmaceutical, Daiichi Sankyo, Janssen Oncology, Genmab, GlaxoSmithKline, Orion Pharma GmbH, Eisai, and BioXCel Therapeutics. DC has received personal fees from Pfizer, Roche, Sanofi, Janssen, Astellas, Bayer, Bristol-Myers Squibb, Merck Sharp and Dohme, Merck Serono, Pierre Fabre, AstraZeneca, and Lilly. BT has received personal fees and research grants from Astellas, Janssen, Sanofi Genzyme, Amgen, and Ferring, and received non-financial support from Sanofi Genzyme. ML has received personal fees from Sanofi, Janssen, Amgen, Bristol-Myers Squibb, MSD Oncology, AstraZeneca, GSK, and Roche. JC has provided an advisory role for Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, MSD Oncology, Johnson and Johnson, Sanofi, Roche, and Pfizer, and has attended speaker bureaus for Asofarma, Astellas, Bayer, and Johnson & Johnson. RI has received honoraria and provided an advisory role for Sanofi, Janssen, Pfizer, Ipsen, Novartis, Bristol-Myers Squibb, and Merck Sharp and Dohme. BM has received travel fees, honoraria and provided an advisory role for Bristol-Myers Squibb and Merck Serono, and received honoraria and provided an advisory role for MSD, Oncology Sanofi, Roche, Janssen, Bayer, Astellas, Amgen, Novartis, Servier, AstraZeneca, Eisai, Eli Lilly, Ipsen, Pierre Fabre, and Pfizer. CH has received consultancy fees for Sanofi, Janssen, and Astellas. SO has received honoraria from Astellas, Bayer, Bristol-Myers Squibb, Janssen, Merck, Novartis, Pfizer, and Sanofi. AO and SB are employees and stockholders of Sanofi. CG-R and EMP are employees of Sanofi. RdW has provided an advisory role for Sanofi, Janssen, Merck, Bayer, Clovis, Astellas, and Roche and received institutional grants from Sanofi and Bayer. CW, ÁS, CT, SF and GF declare no competing interests.
Funding Information:
Research and analysis were supported by Sanofi. The authors were responsible for all content and editorial decisions and received no honoraria for development of this manuscript. Medical writing assistance was provided by Annie Berkley and Amber Wood of Meditech Media, funded by Sanofi.
Publisher Copyright:
© 2020 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - Background: In the CARD study, cabazitaxel significantly improved radiographic progression-free survival and overall survival versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen signalling-targeted inhibitor. Here, we report the quality-of-life outcomes from the CARD study. Methods: CARD was a randomised, multicentre, open-label, phase 4 study involving 62 clinical sites across 13 European countries. Patients (aged ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status ≤2) with confirmed metastatic castration-resistant prostate cancer were randomly assigned (1:1) by means of an interactive voice–web response system to receive cabazitaxel (25 mg/m2 intravenously every 3 weeks, 10 mg daily prednisone, and granulocyte colony-stimulating factor) versus abiraterone (1000 mg orally once daily plus 5 mg prednisone twice daily) or enzalutamide (160 mg orally daily). Stratification factors were ECOG performance status, time to disease progression on the previous androgen signalling-targeted inhibitor, and timing of the previous androgen signalling-targeted inhibitor. The primary endpoint was radiographic progression-free survival; here, we present more detailed analyses of pain (assessed using item 3 on the Brief Pain Inventory-Short Form [BPI-SF]) and symptomatic skeletal events, alongside preplanned patient-reported outcomes, assessed using the Functional Assessment of Cancer Therapy—Prostate (FACT-P) questionnaire and the EuroQoL—5 dimensions, 5 level scale (EQ-5D-5L). Efficacy analyses were done in the intention-to-treat population. Pain response was analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of BPI-SF item 3, and patient-reported outcomes (PROs) were analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of either FACT-P or EQ-5D-5L (PRO population). Analyses of skeletal-related events were also done in the intention-to-treat population. The CARD study is registered with ClinicalTrials.gov, NCT02485691, and is no longer enrolling. Findings: Between Nov 17, 2015, and Nov 28, 2018, of 303 patients screened, 255 were randomly assigned to cabazitaxel (n=129) or abiraterone or enzalutamide (n=126). Median follow-up was 9·2 months (IQR 5·6–13·1). Pain response was observed in 51 (46%) of 111 patients with cabazitaxel and 21 (19%) of 109 patients with abiraterone or enzalutamide (p<0·0001). Median time to pain progression was not estimable (NE; 95% CI NE–NE) with cabazitaxel and 8·5 months (4·9–NE) with abiraterone or enzalutamide (hazard ratio [HR] 0·55, 95% CI 0·32–0·97; log-rank p=0·035). Median time to symptomatic skeletal events was NE (95% CI 20·0–NE) with cabazitaxel and 16·7 months (10·8–NE) with abiraterone or enzalutamide (HR 0·59, 95% CI 0·35–1·01; log-rank p=0·050). Median time to FACT-P total score deterioration was 14·8 months (95% CI 6·3–NE) with cabazitaxel and 8·9 months (6·3–NE) with abiraterone or enzalutamide (HR 0·72, 95% CI 0·44–1·20; log-rank p=0·21). There was a significant treatment effect seen in changes from baseline in EQ-5D-5L utility index score in favour of cabazitaxel over abiraterone or enzalutamide (p=0·030) but no difference between treatment groups for change from baseline in EQ-5D-5L visual analogue scale (p=0·060). Interpretation: Since cabazitaxel improved pain response, time to pain progression, time to symptomatic skeletal events, and EQ-5D-5L utility index, clinicians and patients with metastatic castration-resistant prostate cancer can be reassured that cabazitaxel will not reduce quality of life when compared with treatment with a second androgen signalling-targeted inhibitor. Funding: Sanofi.
AB - Background: In the CARD study, cabazitaxel significantly improved radiographic progression-free survival and overall survival versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen signalling-targeted inhibitor. Here, we report the quality-of-life outcomes from the CARD study. Methods: CARD was a randomised, multicentre, open-label, phase 4 study involving 62 clinical sites across 13 European countries. Patients (aged ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status ≤2) with confirmed metastatic castration-resistant prostate cancer were randomly assigned (1:1) by means of an interactive voice–web response system to receive cabazitaxel (25 mg/m2 intravenously every 3 weeks, 10 mg daily prednisone, and granulocyte colony-stimulating factor) versus abiraterone (1000 mg orally once daily plus 5 mg prednisone twice daily) or enzalutamide (160 mg orally daily). Stratification factors were ECOG performance status, time to disease progression on the previous androgen signalling-targeted inhibitor, and timing of the previous androgen signalling-targeted inhibitor. The primary endpoint was radiographic progression-free survival; here, we present more detailed analyses of pain (assessed using item 3 on the Brief Pain Inventory-Short Form [BPI-SF]) and symptomatic skeletal events, alongside preplanned patient-reported outcomes, assessed using the Functional Assessment of Cancer Therapy—Prostate (FACT-P) questionnaire and the EuroQoL—5 dimensions, 5 level scale (EQ-5D-5L). Efficacy analyses were done in the intention-to-treat population. Pain response was analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of BPI-SF item 3, and patient-reported outcomes (PROs) were analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of either FACT-P or EQ-5D-5L (PRO population). Analyses of skeletal-related events were also done in the intention-to-treat population. The CARD study is registered with ClinicalTrials.gov, NCT02485691, and is no longer enrolling. Findings: Between Nov 17, 2015, and Nov 28, 2018, of 303 patients screened, 255 were randomly assigned to cabazitaxel (n=129) or abiraterone or enzalutamide (n=126). Median follow-up was 9·2 months (IQR 5·6–13·1). Pain response was observed in 51 (46%) of 111 patients with cabazitaxel and 21 (19%) of 109 patients with abiraterone or enzalutamide (p<0·0001). Median time to pain progression was not estimable (NE; 95% CI NE–NE) with cabazitaxel and 8·5 months (4·9–NE) with abiraterone or enzalutamide (hazard ratio [HR] 0·55, 95% CI 0·32–0·97; log-rank p=0·035). Median time to symptomatic skeletal events was NE (95% CI 20·0–NE) with cabazitaxel and 16·7 months (10·8–NE) with abiraterone or enzalutamide (HR 0·59, 95% CI 0·35–1·01; log-rank p=0·050). Median time to FACT-P total score deterioration was 14·8 months (95% CI 6·3–NE) with cabazitaxel and 8·9 months (6·3–NE) with abiraterone or enzalutamide (HR 0·72, 95% CI 0·44–1·20; log-rank p=0·21). There was a significant treatment effect seen in changes from baseline in EQ-5D-5L utility index score in favour of cabazitaxel over abiraterone or enzalutamide (p=0·030) but no difference between treatment groups for change from baseline in EQ-5D-5L visual analogue scale (p=0·060). Interpretation: Since cabazitaxel improved pain response, time to pain progression, time to symptomatic skeletal events, and EQ-5D-5L utility index, clinicians and patients with metastatic castration-resistant prostate cancer can be reassured that cabazitaxel will not reduce quality of life when compared with treatment with a second androgen signalling-targeted inhibitor. Funding: Sanofi.
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U2 - 10.1016/S1470-2045(20)30449-6
DO - 10.1016/S1470-2045(20)30449-6
M3 - Article
C2 - 32926841
AN - SCOPUS:85094838543
VL - 21
SP - 1513
EP - 1525
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 11
ER -