Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. (28th February 2022)

• Record Type: Journal Article
• Authors: Matsubara, Nobuaki; Nishimura, Kazuo; Kawakami, Satoru; Joung, Jae Young; Uemura, Hiroji; Goto, Takayuki; Kwon, Tae Gyun; Sugimoto, Mikio; Kato, Masashi; Wang, Shian-Shiang; Pang, See-Tong; Chen, Chung-Hsin; Fujita, Tomoko; Nii, Masahiro; Shen, Liji; Dujka, Melanie; Hussain, Maha; de Bono, Johann
• Is Part Of: Japanese journal of clinical oncology. Volume 52:Number 5(2022)
• Page Start: 441
• Page End: 448
• Publication Date: 2022-02-28
• Subjects: BRCA -- homologous recombination repair gene alteration -- mCRPC -- PROfound -- olaparib; Oncology -- Periodicals; Cancer -- Periodicals; 616.994005
• DOI: 10.1093/jjco/hyac015
• Languages: English
• ISSNs: 0368-2811

Abstract

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 Abstract : Results of the exploratory analyses presented here suggest that olaparib improved outcomes for Asian patients in the PROfound trial versus control. The safety and tolerability of olaparib in Asian patients were similar to the PROfound global population.