Background: In the CARD study (NCT02485691), cabazitaxel significantly improved median radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel and progressed ≤12 mo on the alternative agent (abiraterone/enzalutamide). Objective: To assess cabazitaxel versus abiraterone/enzalutamide in older (≥70 yr) and younger (<70 yr) patients in CARD. Design, setting, and participants: Patients with mCRPC were randomized 1:1 to cabazitaxel (25 mg/m2 plus prednisone and granulocyte colony-stimulating factor) versus abiraterone (1000 mg plus prednisone) or enzalutamide (160 mg). Outcome measurements and statistical analysis: Analyses of rPFS (primary endpoint) and safety by age were prespecified; others were post hoc. Treatment groups were compared using stratified log-rank or Cochran–Mantel-Haenszel tests. Results and limitations: Of the 255 patients randomized, 135 were aged ≥70 yr (median 76 yr). Cabazitaxel, compared with abiraterone/enzalutamide, significantly improved median rPFS in older (8.2 vs 4.5 mo; hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.38–0.89; p = 0.012) and younger (7.4 vs 3.2 mo; HR = 0.47; 95% CI = 0.30–0.74; p < 0.001) patients. The median OS of cabazitaxel versus abiraterone/enzalutamide was 13.9 versus 9.4 mo in older patients (HR = 0.66; 95% CI = 0.41–1.06; p = 0.084), and it was 13.6 versus 11.8 mo in younger patients (HR = 0.66; 95% CI = 0.41–1.08; p = 0.093). Progression-free survival, prostate-specific antigen, and tumor and pain responses favored cabazitaxel, regardless of age. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 58% versus 49% of older patients receiving cabazitaxel versus abiraterone/enzalutamide and 48% versus 42% of younger patients. In older patients, cardiac adverse events were more frequent with abiraterone/enzalutamide; asthenia and diarrhea were more frequent with cabazitaxel. Conclusions: Cabazitaxel improved efficacy outcomes versus abiraterone/enzalutamide in patients with mCRPC after prior docetaxel and abiraterone/enzalutamide, regardless of age. TEAEs were more frequent among older patients. The cabazitaxel safety profile was manageable across age groups. Patient summary: Clinical trial data showed that cabazitaxel improved survival versus abiraterone/enzalutamide with manageable side effects in patients with metastatic castration-resistant prostate cancer who had previously received docetaxel and the alternative agent (abiraterone/enzalutamide), irrespective of age.
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Financial disclosures: Cora N. Sternberg certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Cora N. Sternberg has provided a consulting or advisory role for Bayer, Merck Sharp & Dohme, Pfizer, Roche, Incyte, AstraZeneca, Sanofi, Merck Serono, Medscape, UroToday, Janssen, Immunomedics (now Gilead), Astellas Pharma, and BMS. Daniel Castellano has provided a consultancy or advisory role for Janssen, Roche, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, BMS, MSD, Bayer, Lilly, Sanofi, Pierre Fabre, and Boehringer Ingelheim; received travel/accommodation/expenses from Pfizer, Roche, BMS, and AstraZeneca; and received research funding from Janssen. Johann de Bono has provided a consulting or advisory role for AstraZeneca, Sanofi, Roche, Astellas Pharma, Bayer, Pfizer, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim, Sierra Oncology, Menarini Silicon Biosystems, Celgene, Taiho Pharmaceuticals, Daiichi Sankyo, Janssen, Genmab, GSK, Orion Pharma GmbH, Eisai, and BioXCel therapeutics; received travel/accommodation/expenses from AstraZeneca, Astellas Pharma, GSK, Orion Pharma GmbH, Sanofi, Genmab, Taiho Pharmaceuticals, Qiagen, and Vertex; is associated with patents/royalties/other IP for abiraterone, PARP inhibitors, IL-23 targeting in prostate cancer, CHK1 inhibitor; and received honoraria and/or research funding from AstraZeneca, Sanofi, Astellas Pharma, Pfizer, Roche/Genentech, Janssen, Menarini Silicon Biosystems, Daiichi Sankyo, Sierra Oncology, Taiho Pharmaceuticals, Merck Serono, Astex Pharmaceuticals, Merck Sharp & Dohme, Orion Pharma GmbH, CellCentric, Celgene, Bayer, MedImmune, Medivation, and BioExcel. Karim Fizazi has provided a consulting or advisory role for Janssen, Bayer, Astellas Pharma, Sanofi, Orion Pharma GmbH, Curevac, AstraZeneca, ESSA and Amgen; received travel/accommodation/expenses from Amgen and Janssen; and received honoraria from Janssen, Sanofi, Astellas, and Bayer. Bertrand Tombal has provided a consulting or advisory role for Astellas Pharma, Bayer, Ferring, Janssen, Takeda, Steba Biotech, Sanofi, and Amgen; received travel/accommodation/expenses from Amgen, Astellas Pharma, Bayer, Ferring, Janssen, and Sanofi; and received honoraria and/or research funding from Amgen, Astellas Pharma, Bayer, Ferring, Sanofi, Janssen, Pfizer, and Myovant Sciences. Gero Kramer has received honoraria and/or research funding from Sanofi, Bayer, Takeda, Astellas Pharma, Janssen, Ipsen, AstraZeneca, and Novartis. Jean-Christophe Eymard has a leadership role with Sanofi and has received honoraria from Sanofi. Aristotelis Bamias has provided a consulting or advisory role for BMS, Pfizer, AstraZeneca, MSD, Roche, and Ferring, and received honoraria and/or research funding from BMS, MSD, Astellas Pharma, Sanofi, Debiopharm Roche, AstraZeneca, and Pfizer. Joan Carles has provided a consulting or advisory role for Bayer, J&J, BMS, Astellas Pharma, Pfizer, Sanofi, MSD Oncology, Roche, Asofarma, and AstraZeneca; received travel/accommodation/expenses from BMS, Ipsen, Roche, and AstraZeneca; and received research funding from AB Science, Aragon Pharmaceuticals, Arog, Astellas Pharma, AVEO, Bayer, Blueprint Medicines, Boehringer Ingelheim, BMS, Clovis Oncology, Cougar Biotechnology, Deciphera, Exelixis, Roche/Genentech, GSK, Incyte, Janssen-Cilag, Karyopharm Therapeutics, Medimmune, Millennium, Nanobiotix, Novartis, Pfizer, Puma Biotechnology, Sanofi, SFJ Pharmaceuticals Group, Teva, Mediolanum Laboratories Leurquin, Lilly, and AstraZeneca. Roberto Iacovelli has received honoraria from Sanofi, Janssen, Pfizer, Ipsen, Novartis, BMS, and MSD. Bohuslav Melichar has received honoraria from BMS, MSD, Novartis, Merck Serono, Sanofi, Roche, Janssen, Bayer, Astellas Pharma, SERVIER, Amgen, and Pfizer. Elizabeth M. Poole, Ayse Ozatilgan, and Christine Geffriaud-Ricouard are employed by Sanofi, and may hold shares and/or stock options in the company. Ronald de Wit has provided a consulting or advisory role for Sanofi, Merck Sharp & Dohme, Roche/Genetech, Janssen, Bayer, and Clovis Oncology; received travel/accommodation/expenses from Lilly; and received honoraria and/or research funding from Sanofi, Merck Sharp & Dohme, and Bayer. Christian Wülfing, Ásgerður Sverrisdóttir, Christine Theodore, Susan Feyerabend, and Carole Helissey have no disclosures.