Het resultaat van de studie LATITUDE, A phase III, double-blind, randomized trial of androgen deprivation therapy with abiraterone acetate plus prednisone or placebos in newly diagnosed high-risk metastatic hormone-naive prostate cancer is hét belangrijkste item op het gebied van mCRPC op de ASCO 2017. DUOS berichtte reeds over de studie waaruit bleek dat abiraterone toegevoegd aan ADT de overlevingswinst significant doet toenemen, op 27 mei jl. Onderstaand treft u de, inmiddels vrijgegeven, abstract van LATITUDE.
Background: Pts with newly diagnosed mHNPC, particularly with high-risk characteristics, have a poor prognosis. ADT+docetaxel showed improved outcomes in mHNPC, but many pts are not candidates for docetaxel and may benefit from alternative therapy. AA+P is indicated for metastatic castration-resistant prostate cancer pts. LATITUDE evaluates clinical benefit of early intervention with AA+P added to ADT in newly diagnosed, high-risk mHNPC pts.
Methods: 1199 pts with newly diagnosed (≤ 3 mos prior to randomization) mHNPC (ECOG PS 0-2) with ≥ 2 of 3 risk factors (Gleason ≥ 8, ≥ 3 bone lesions, measurable visceral metastases) were randomized 1:1 to ADT+AA (1 g QD) + P (5 mg QD) or ADT+PBOs of AA and P. Co-primary end points were overall survival (OS) and radiographic progression-free survival (rPFS). One rPFS (~565 events), 2 interim, and 1 final OS analyses (~426, ~554, and ~852 events) were planned.
Results: At this first interim analysis (median follow-up of 30.4 mos; 406 deaths [48%]; 593 rPFS events), OS, rPFS, and all secondary end points significantly favored ADT+AA+P (Table). The IDMC unanimously recommended unblinding the study and crossing pts to ADT+AA+P. Grade 3/4 adverse events (ADT+AA+P vs ADT+PBOs) (%): hypertension (20.3 vs 10.0); hypokalemia (10.4 vs 1.3); increased ALT (5.5 vs 1.3) or AST (4.4 vs 1.5).
Conclusions: Early use of AA+P added to ADT in pts with high-risk mHNPC yielded significantly improved OS, rPFS, and all secondary end points vs ADT+PBOs alone. ADT+AA+P had a favorable risk/benefit ratio and supports early intervention with AA+P in newly diagnosed, high-risk mHNPC. Clinical trial information: NCT01715285
|ADT+ AA+P (n=597)||ADT+ PBOs (n=602)||HR (95% CI)||p value|
|Co-primary end points|
|Secondary end points|
|Pain progression||NR||16.6||0.70 (0.58-0.83)||<0.0001|
|PSA progression||33.2||7.4||0.30 (0.26-0.35)|
|Symptomatic skeletal-related event||NR||NR||0.70 (0.54-0.92)||0.0086|
|Subsequent PC therapy||NR||21.6||0.42 (0.35-0.50)|
NR, not reached.