Olaparib/abiraterone regimen approved in Japan for BRCA-positive mCRPC
The approval of the olaparib/abiraterone regimen was based on an exploratory subgroup analysis of the phase 3 PROpel trial consisting of the 85 patients in the study with BRCA-positive metastatic castration-resistant prostate cancer.
The Japanese Ministry of Health, Labor and Welfare has approved olaparib (Lynparza) for use in combination with abiraterone acetate (Zytiga) and prednisolone for the treatment of adult patients with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC).1
“The PROpel trial showed that the combination of Lynparza plus abiraterone delivered clinically meaningful improvements in outcomes for patients with BRCA-mutation mCRPC. With this approval, patients in Japan will now have the opportunity to benefit from this new treatment combination which has the potential to become the new standard of care for patients with BRCA mutations,” Mototsugu Oya, professor and chairman, department of urology, Keio University School of Medicine, Japan, stated in a press release.
The approval was based on an exploratory subgroup analysis of the phase 3 PROpel trial (NCT03732820) consisting of the 85 patients in the study with BRCA-positive mCRPC. In this subgroup, the addition of olaparib to abiraterone and prednisone/prednisolone led to a 77% reduction in the risk of disease progression or death vs abiraterone plus prednisone/prednisolone alone (HR, 0.23). The olaparib addition also led to a 61% reduction in the risk of death (HR, 0.39).1
The median radiographic progression-free survival (rPFS) was not reached in the olaparibarm compared to 8.4 months in the control arm. The median overall survival (OS) was not reached vs 23.6 months in the olaparib and control groups, respectively.1
There were no new safety or tolerability signals in the olaparib arm compared with prior research with the individual treatments. In the overall ITT population of PROpel the most frequently occurring adverse events in the olaparib arm were anemia (45.5%), nausea (28.1%), and fatigue (27.9%).1
“The PROpel trial showed that the combination of Lynparza plus abiraterone delivered clinically meaningful improvements in outcomes for patients with BRCA-mutation mCRPC. With this approval, patients in Japan will now have the opportunity to benefit from this new treatment combination which has the potential to become the new standard of care for patients with BRCA mutations,” Mototsugu Oya, professor and chairman, department of urology, Keio University School of Medicine, Japan, stated in a press release.
Overall PROpel trial
The international, double-blind, phase 3 PROpel trial randomized patients with mCRPC in the first-line setting 1:1 to receive olaparib at 300 mg twice daily plus abiraterone at 1000 mg daily (n = 399) or placebo and abiraterone at 1000 mg daily (n = 397). Patients could have received docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting, but no prior abiraterone was allowed. Other NHAs were permitted if they were stopped at least 12 months prior to study enrollment. Patients also had ongoing androgen deprivation therapy and an ECOG performance status of 0 or 1.2
Baseline characteristics were well-balanced between the 2 arms. The median age was 69.5 years (range, 43-91), and most patients had an ECOG performance status of 0 (70.1%). Of note, symptomatic patients (Brief Pain Inventory-Short Form ≥4 and/or opiate use) comprised 25.8% and 20.2% of olaparib- and placebo-treated patients, respectively; 22.5% of patients had received docetaxel at the mHSPC stage.
In the overall ITT population, the median investigator-assessed rPFS was 24.8 months with olaparib/abiraterone vs 16.6 months with placebo/abiraterone, translating to a 34% reduction in the risk of radiographic disease progression or death (HR, 0.66; 95% CI, 0.54-0.81; P <.0001).2
Data from the final prespecified OS analysis for the ITT population showed that the median OS was 42.1 months in the abiraterone/olaparib cohort vs 34.7 months in the abiraterone/placebo cohort, translating to a 19% reduction in the risk of death (HR, 0.81; 95% CI, 0.67-1.00; P = .0544). The maturity for survival was 47.9%. The results were not statistically significant.3
In the United States, olaparib plus abiraterone and prednisone/prednisolone is approved by the FDA for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated mCRPC, as determined by an FDA-approved companion diagnostic test.4
References
1. LYNPARZA® (olaparib) Plus Abiraterone and Prednisone or Prednisolone Approved in Japan for the Treatment of BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer. Published online and accessed August 24, 2023. https://www.businesswire.com/news/home/20230824404671/en/LYNPARZA%C2%AE-olaparib-Plus-Abiraterone-and-Prednisone-or-Prednisolone-Approved-in-Japan-for-the-Treatment-of-BRCA-Mutated-Metastatic-Castration-Resistant-Prostate-Cancer
2. Clarke NW, Armstrong AJ, Thiery Vuillemin A, et al; PROpel Investigators. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid. 2022;1(9). doi:10.1056/EVIDoa2200043
3. Clarke NW, Armstrong AJ, Thiery Vuillemin A, et al. Final overall survival (OS) in PROpel: abiraterone (abi) and olaparib (ola) versus abiraterone and placebo (pbo) as first-line (1L) therapy for metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2023;41(suppl 6):LBA16. doi:10.1200/JCO.2023.41.6_suppl.LBA16
4. FDA approves olaparib with abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer. Accessed May 31, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-abiraterone-and-prednisone-or-prednisolone-brca-mutated-metastatic-castration
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