TY - JOUR
T1 - Olaparib in patients with mCRPC with homologous recombination repair gene alterations
T2 - PROfound Asian subset analysis
AU - Matsubara, Nobuaki
AU - Nishimura, Kazuo
AU - Kawakami, Satoru
AU - Joung, Jae Young
AU - Uemura, Hiroji
AU - Goto, Takayuki
AU - Kwon, Tae Gyun
AU - Sugimoto, Mikio
AU - Kato, Masashi
AU - Wang, Shian Shiang
AU - Pang, See Tong
AU - Chen, Chung Hsin
AU - Fujita, Tomoko
AU - Nii, Masahiro
AU - Shen, Liji
AU - Dujka, Melanie
AU - Hussain, Maha
AU - De Bono, Johann
N1 - Funding Information:
This work was supported by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp., a sub-sidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Publisher Copyright:
© 2022 The Author(s).
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Background: The Phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control; randomized 2:1 to olaparib or control) in men with homologous recombination repair gene alterations and metastatic castration-resistant prostate cancer whose disease progressed on prior next-generation hormonal agent. Methods: We present efficacy and safety data from an exploratory post hoc analysis of olaparib in the PROfound Asian subset. Analyses were not planned, alpha controlled or powered. Of 101 Asian patients enrolled in Japan (n=57), South Korea (n=29) and Taiwan (n=15), 66 and 35 patients received olaparib and control, respectively. Results: Radiographic progression-free survival (rPFS) and overall survival (OS) favored olaparib versus control in Cohort A [rPFS 7.2 vs. 4.5 months, HR 0.58, 95% CI 0.29-1.21, P = 0.14 (nominal); OS 23.4 vs. 17.8 months, HR 0.81, 95% CI 0.40-1.74, P = 0.57 (nominal)] and Cohorts A+B [rPFS 5.8 vs. 3.5 months, HR 0.69, 95% CI 0.42-1.16, P = 0.13 (nominal); OS 18.6 vs. 16.2 months, HR 0.96, 95% CI 0.56-1.70, P = 0.9 (nominal)]. Olaparib showed greatest improvement in patients harboring BRCA alterations [rPFS 9.3 vs. 3.5 months, HR 0.17, 95% CI 0.06-0.49, P = 0.0003 (nominal); OS 26.8 vs. 14.3 months, HR 0.62, 95% CI 0.24-1.79, P = 0.34 (nominal)]. Safety data were consistent with the known profile of olaparib, with no new safety signals identified. Conclusion: In PROfound, there was a statistically significant improvement in outcomes reported in the global population of patients with metastatic castration-resistant prostate cancer and alterations in homologous recombination repair genes whose disease progressed on prior next-generation hormonal agent compared with control. For the subset of Asian patients reported here, exploratory analysis suggested that there was also an improvement in outcomes versus control. The safety and tolerability of olaparib in Asian patients were similar to that of the PROfound global population.
AB - Background: The Phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control; randomized 2:1 to olaparib or control) in men with homologous recombination repair gene alterations and metastatic castration-resistant prostate cancer whose disease progressed on prior next-generation hormonal agent. Methods: We present efficacy and safety data from an exploratory post hoc analysis of olaparib in the PROfound Asian subset. Analyses were not planned, alpha controlled or powered. Of 101 Asian patients enrolled in Japan (n=57), South Korea (n=29) and Taiwan (n=15), 66 and 35 patients received olaparib and control, respectively. Results: Radiographic progression-free survival (rPFS) and overall survival (OS) favored olaparib versus control in Cohort A [rPFS 7.2 vs. 4.5 months, HR 0.58, 95% CI 0.29-1.21, P = 0.14 (nominal); OS 23.4 vs. 17.8 months, HR 0.81, 95% CI 0.40-1.74, P = 0.57 (nominal)] and Cohorts A+B [rPFS 5.8 vs. 3.5 months, HR 0.69, 95% CI 0.42-1.16, P = 0.13 (nominal); OS 18.6 vs. 16.2 months, HR 0.96, 95% CI 0.56-1.70, P = 0.9 (nominal)]. Olaparib showed greatest improvement in patients harboring BRCA alterations [rPFS 9.3 vs. 3.5 months, HR 0.17, 95% CI 0.06-0.49, P = 0.0003 (nominal); OS 26.8 vs. 14.3 months, HR 0.62, 95% CI 0.24-1.79, P = 0.34 (nominal)]. Safety data were consistent with the known profile of olaparib, with no new safety signals identified. Conclusion: In PROfound, there was a statistically significant improvement in outcomes reported in the global population of patients with metastatic castration-resistant prostate cancer and alterations in homologous recombination repair genes whose disease progressed on prior next-generation hormonal agent compared with control. For the subset of Asian patients reported here, exploratory analysis suggested that there was also an improvement in outcomes versus control. The safety and tolerability of olaparib in Asian patients were similar to that of the PROfound global population.
KW - BRCA
KW - PROfound
KW - homologous recombination repair gene alteration
KW - mCRPC
KW - olaparib
UR - http://www.scopus.com/inward/record.url?scp=85129998422&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129998422&partnerID=8YFLogxK
U2 - 10.1093/jjco/hyac015
DO - 10.1093/jjco/hyac015
M3 - Article
C2 - 35229141
AN - SCOPUS:85129998422
SN - 0368-2811
VL - 52
SP - 441
EP - 448
JO - Japanese Journal of Clinical Oncology
JF - Japanese Journal of Clinical Oncology
IS - 5
ER -
