TY - JOUR
T1 - Randomized Phase III Study of Enzalutamide Compared With Enzalutamide Plus Abiraterone for Metastatic Castration-Resistant Prostate Cancer (Alliance A031201 Trial)
AU - Morris, Michael J.
AU - Heller, Glenn
AU - Hillman, David W.
AU - Bobek, Olivia
AU - Ryan, Charles
AU - Antonarakis, Emmanuel S.
AU - Bryce, Alan H.
AU - Hahn, Olwen
AU - Beltran, Himisha
AU - Armstrong, Andrew J.
AU - Schwartz, Lawrence
AU - Lewis, Lionel D.
AU - Beumer, Jan H.
AU - Langevin, Brooke
AU - Mcgary, Eric C.
AU - Mehan, Paul T.
AU - Goldkorn, Amir
AU - Roth, Bruce J.
AU - Xiao, Han
AU - Watt, Colleen
AU - Taplin, Mary Ellen
AU - Halabi, Susan
AU - Small, Eric J.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/6/20
Y1 - 2023/6/20
N2 - PURPOSEEnzalutamide and abiraterone both target androgen receptor signaling but via different mechanisms. The mechanism of action of one drug may counteract the resistance pathways of the other. We sought to determine whether the addition of abiraterone acetate and prednisone (AAP) to enzalutamide prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the first-line setting.PATIENTS AND METHODSMen with untreated mCRPC were randomly assigned (1:1) to receive first-line enzalutamide with or without AAP. The primary end point was OS. Toxicity, prostate-specific antigen declines, pharmacokinetics, and radiographic progression-free survival (rPFS) were also examined. Data were analyzed using an intent-to-treat approach. The Kaplan-Meier estimate and the stratified log-rank statistic were used to compare OS between treatments.RESULTSIn total, 1,311 patients were randomly assigned: 657 to enzalutamide and 654 to enzalutamide plus AAP. OS was not statistically different between the two arms (median, 32.7 [95% CI, 30.5 to 35.4] months for enzalutamide v 34.2 [95% CI, 31.4 to 37.3] months for enzalutamide and AAP; hazard ratio [HR], 0.89; one-sided P =.03; boundary nominal significance level =.02). rPFS was longer in the combination arm (median rPFS, 21.3 [95% CI, 19.4 to 22.9] months for enzalutamide v 24.3 [95% CI, 22.3 to 26.7] months for enzalutamide and AAP; HR, 0.86; two-sided P =.02). However, pharmacokinetic clearance of abiraterone was 2.2- to 2.9-fold higher when administered with enzalutamide, compared with clearance values for abiraterone alone.CONCLUSIONThe addition of AAP to enzalutamide for first-line treatment of mCRPC was not associated with a statistically significant benefit in OS. Drug-drug interactions between the two agents resulting in increased abiraterone clearance may partly account for this result, although these interactions did not prevent the combination regimen from having more nonhematologic toxicity.
AB - PURPOSEEnzalutamide and abiraterone both target androgen receptor signaling but via different mechanisms. The mechanism of action of one drug may counteract the resistance pathways of the other. We sought to determine whether the addition of abiraterone acetate and prednisone (AAP) to enzalutamide prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the first-line setting.PATIENTS AND METHODSMen with untreated mCRPC were randomly assigned (1:1) to receive first-line enzalutamide with or without AAP. The primary end point was OS. Toxicity, prostate-specific antigen declines, pharmacokinetics, and radiographic progression-free survival (rPFS) were also examined. Data were analyzed using an intent-to-treat approach. The Kaplan-Meier estimate and the stratified log-rank statistic were used to compare OS between treatments.RESULTSIn total, 1,311 patients were randomly assigned: 657 to enzalutamide and 654 to enzalutamide plus AAP. OS was not statistically different between the two arms (median, 32.7 [95% CI, 30.5 to 35.4] months for enzalutamide v 34.2 [95% CI, 31.4 to 37.3] months for enzalutamide and AAP; hazard ratio [HR], 0.89; one-sided P =.03; boundary nominal significance level =.02). rPFS was longer in the combination arm (median rPFS, 21.3 [95% CI, 19.4 to 22.9] months for enzalutamide v 24.3 [95% CI, 22.3 to 26.7] months for enzalutamide and AAP; HR, 0.86; two-sided P =.02). However, pharmacokinetic clearance of abiraterone was 2.2- to 2.9-fold higher when administered with enzalutamide, compared with clearance values for abiraterone alone.CONCLUSIONThe addition of AAP to enzalutamide for first-line treatment of mCRPC was not associated with a statistically significant benefit in OS. Drug-drug interactions between the two agents resulting in increased abiraterone clearance may partly account for this result, although these interactions did not prevent the combination regimen from having more nonhematologic toxicity.
UR - http://www.scopus.com/inward/record.url?scp=85161877879&partnerID=8YFLogxK
U2 - 10.1200/JCO.22.02394
DO - 10.1200/JCO.22.02394
M3 - Article
C2 - 36996380
AN - SCOPUS:85161877879
SN - 0732-183X
VL - 41
SP - 3352
EP - 3362
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 18
ER -