Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis

Nobuaki Matsubara; Kazuo Nishimura; Satoru Kawakami; Jae Young Joung; Hiroji Uemura; Takayuki Goto; Tae Gyun Kwon; Mikio Sugimoto; Masashi Kato; Shian-Shiang Wang; See-Tong Pang; Chung-Hsin Chen; Tomoko Fujita; Masahiro Nii; Liji Shen; Melanie Dujka; Maha Hussain; Johann de Bono

doi:10.1093/jjco/hyac015

Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis

Jpn J Clin Oncol. 2022 May 5;52(5):441-448. doi: 10.1093/jjco/hyac015.

Authors

Nobuaki Matsubara¹, Kazuo Nishimura², Satoru Kawakami³, Jae Young Joung⁴, Hiroji Uemura⁵, Takayuki Goto⁶, Tae Gyun Kwon⁷, Mikio Sugimoto⁸, Masashi Kato⁹, Shian-Shiang Wang¹⁰, See-Tong Pang¹¹, Chung-Hsin Chen¹², Tomoko Fujita¹³, Masahiro Nii¹³, Liji Shen¹⁴, Melanie Dujka¹⁵, Maha Hussain¹⁶, Johann de Bono¹⁷

Affiliations

¹ National Cancer Center Hospital East, Chiba, Japan.
² Osaka International Cancer Institute, Osaka, Japan.
³ Saitama Medical University Saitama Medical Center, Saitama, Japan.
⁴ National Cancer Center, Goyang-si, South Korea.
⁵ Yokohama City University Medical Center, Yokohama, Japan.
⁶ Department of Urology, Kyoto University Hospital, Kyoto, Japan.
⁷ Chilgok Kyungpook National University Medical Center, Daegu, South Korea.
⁸ Department of Urology, Kagawa University Hospital, Kagawa, Japan.
⁹ Department of Urology, Nagoya University Hospital, Nagoya, Japan.
¹⁰ Division of Urology, Department of Surgery, Veterans General Hospital Taichung, Taichung, Taiwan.
¹¹ Department of Uro-oncology, Chang Gung Medical Foundation-LinKou Branch, Taoyuan City, Taiwan.
¹² Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
¹³ AstraZeneca, Osaka, Japan.
¹⁴ Merck & Co., Inc., Kenilworth, NJ, USA.
¹⁵ AstraZeneca, Gaithersburg, MD, USA.
¹⁶ Division of Hematology-Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁷ Drug Development Unit, Institute of Cancer Research and Royal Marsden Hospital, London, UK.

Abstract

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.

Clinical trial number: ClinicalTrials.gov NCT02987543.

Keywords: BRCA; PROfound; homologous recombination repair gene alteration; mCRPC; olaparib.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial

MeSH terms

Antineoplastic Combined Chemotherapy Protocols
Humans
Male
Phthalazines / adverse effects
Piperazines / adverse effects
Prostatic Neoplasms, Castration-Resistant* / drug therapy
Prostatic Neoplasms, Castration-Resistant* / genetics
Prostatic Neoplasms, Castration-Resistant* / pathology
Recombinational DNA Repair

Substances

Phthalazines
Piperazines
olaparib

Associated data

ClinicalTrials.gov/NCT02987543

Grants and funding

AstraZeneca