TY - JOUR
TI - Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer
AU - De Wit, R.
AU - De Bono, J.
AU - Sternberg, C.N.
AU - Fizazi, K.
AU - Tombal, B.
AU - Wülfing, C.
AU - Kramer, G.
AU - Eymard, J.-C.
AU - Bamias, A.
AU - Carles, J.
AU - Iacovelli, R.
AU - Melichar, B.
AU - Sverrisdóttir, Á.
AU - Theodore, C.
AU - Feyerabend, S.
AU - Helissey, C.
AU - Ozatilgan, A.
AU - Geffriaud-Ricouard, C.
AU - Castellano, D.
JO - The New England journal of medicine
PY - 2019
VL - 381
TODO - 26
SP - 2506-2518
PB - Massachussetts Medical Society
SN - null
TODO - 10.1056/NEJMoa1911206
TODO - abiraterone;  alanine aminotransferase;  antihistaminic agent;  aspartate aminotransferase;  cabazitaxel;  dexamethasone;  docetaxel;  enzalutamide;  granulocyte colony stimulating factor;  prednisone;  prostate specific antigen;  abiraterone;  androstane derivative;  antiandrogen;  antineoplastic agent;  cabazitaxel;  enzalutamide;  phenylthiohydantoin;  prednisone;  taxoid, abdominal pain;  acute kidney failure;  adult;  aged;  alanine aminotransferase blood level;  alopecia;  anemia;  anxiety disorder;  arthralgia;  Article;  aspartate aminotransferase blood level;  asthenia;  backache;  bladder disease;  body weight disorder;  cancer growth;  cancer mortality;  cancer survival;  castration resistant prostate cancer;  clinical effectiveness;  confusion;  constipation;  controlled study;  decreased appetite;  depression;  descriptive research;  diarrhea;  disorientation;  drug safety;  dysgeusia;  dyspnea;  dysuria;  fatigue;  febrile neutropenia;  flank pain;  follow up;  fracture;  heart disease;  hematuria;  human;  hydronephrosis;  hypertension;  hypokalemia;  infection;  kidney disease;  kidney failure;  leukopenia;  lower urinary tract symptom;  major clinical study;  male;  mental disease;  micturition disorder;  multicenter study;  musculoskeletal pain;  nausea;  neck pain;  neutropenia;  open study;  overall survival;  peripheral edema;  peripheral neuropathy;  pollakisuria;  priority journal;  progression free survival;  quality of life;  radiculopathy;  randomized controlled trial;  response evaluation criteria in solid tumors;  sciatica;  side effect;  sleep disorder;  spinal cord compression;  spinal cord disease;  stomatitis;  thrombocytopenia;  treatment duration;  treatment withdrawal;  urethra disease;  urine incontinence;  urine retention;  very elderly;  vomiting;  castration resistant prostate cancer;  clinical trial;  comparative study;  intravenous drug administration;  Kaplan Meier method;  middle aged;  mortality, Aged;  Aged, 80 and over;  Androgen Antagonists;  Androstenes;  Antineoplastic Combined Chemotherapy Protocols;  Humans;  Infusions, Intravenous;  Kaplan-Meier Estimate;  Male;  Middle Aged;  Phenylthiohydantoin;  Prednisone;  Progression-Free Survival;  Prostatic Neoplasms, Castration-Resistant;  Taxoids
TODO - BACKGROUND The efficacy and safety of cabazitaxel, as compared with an androgen-signaling–targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who were previously treated with docetaxel and had progression within 12 months while receiving the alternative inhibitor (abiraterone or enzalutamide) are unclear. METHODS We randomly assigned, in a 1:1 ratio, patients who had previously received docetaxel and an androgen-signaling–targeted inhibitor (abiraterone or enzalutamide) to receive cabazitaxel (at a dose of 25 mg per square meter of body-surface area intravenously every 3 weeks, plus prednisone daily and granulocyte colony-stimulating factor) or the other androgen-signaling–targeted inhibitor (either 1000 mg of abiraterone plus prednisone daily or 160 mg of enzalutamide daily). The primary end point was imaging-based progression-free survival. Secondary end points of survival, response, and safety were assessed. RESULTS A total of 255 patients underwent randomization. After a median follow-up of 9.2 months, imaging-based progression or death was reported in 95 of 129 patients (73.6%) in the cabazitaxel group, as compared with 101 of 126 patients (80.2%) in the group that received an androgen-signaling–targeted inhibitor (hazard ratio, 0.54; 95% confidence interval [CI], 0.40 to 0.73; P<0.001). The median imaging-based progression-free survival was 8.0 months with cabazitaxel and 3.7 months with the androgen-signaling–targeted inhibitor. The median overall survival was 13.6 months with cabazitaxel and 11.0 months with the androgen-signaling–targeted inhibitor (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.89; P=0.008). The median progression-free survival was 4.4 months with cabazitaxel and 2.7 months with an androgen-signaling–targeted inhibitor (hazard ratio for progression or death, 0.52; 95% CI, 0.40 to 0.68; P<0.001), a prostate-specific antigen response occurred in 35.7% and 13.5% of the patients, respectively (P<0.001), and tumor response was noted in 36.5% and 11.5% (P=0.004). Adverse events of grade 3 or higher occurred in 56.3% of patients receiving cabazitaxel and in 52.4% of those receiving an androgen-signaling–targeted inhibitor. No new safety signals were observed. CONCLUSIONS Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling–targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who had been previously treated with docetaxel and the alternative androgen-signaling–targeted agent (abiraterone or enzalutamide). Copyright © 2019 Massachusetts Medical Society.
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