Τίτλος:
Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
De Wit, R.
De Bono, J.
Sternberg, C.N.
Fizazi, K.
Tombal, B.
Wülfing, C.
Kramer, G.
Eymard, J.-C.
Bamias, A.
Carles, J.
Iacovelli, R.
Melichar, B.
Sverrisdóttir, Á.
Theodore, C.
Feyerabend, S.
Helissey, C.
Ozatilgan, A.
Geffriaud-Ricouard, C.
Castellano, D.
Περιοδικό:
The New England journal of medicine
Εκδότης:
Massachussetts Medical Society
Λέξεις-κλειδιά:
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
DOI:
10.1056/NEJMoa1911206
