The Chinese National Medical Products Administration has issued a conditional approval of the PARP inhibitor olaparib (Lynparza) for the treatment of adult patients with germline or somatic BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment that included a novel hormonal agent (abiraterone acetate [Zytiga], enzalutamide [Xtandi]).1
The approval is based on a subgroup analysis of the pivotal phase 3 PROfound trial, in which olaparib reduced the risk of death by 37% (HR, 0.63) versus abiraterone or enzalutamide in men with mCRPC harboring BRCA1/2 mutations. The PARP inhibitor also reduced the risk of disease progression or death by 78% (HR = 0.22; P <.0001) versus the control arm.
The continued approval of olaparib in China is contingent on the treatment demonstrating a clinical benefit in Chinese patients enrolled in a planned bridging trial.
“The approval underscores the critical importance of BRCA testing in men with prostate cancer. We are proud to provide a new personalized treatment option for men with this devastating disease in China, and we will continue to collaborate with the Chinese government and healthcare organizations to bring Lynparza to patients who need it,” Roy Baynes, MD, PhD,
senior vice president and head of global clinical development, chief medical officer, Merck, which codevelops olaparib with AstraZeneca, stated in a press release.
Overall, the PROfound trial enrolled patients with mCRPC who had alterations in at least 1 of 15 prespecified genes with a direct or indirect role in homologous recombination repair (HRR) and whose disease had progressed during previous treatment with a next-generation hormonal agents.
Cohort A (n = 245) consisted of patients with at least 1 alteration in BRCA1, BRCA2, or ATM, while cohort B (n = 142) comprised patients with at least one alteration in any of the other 12 prespecified genes.
Patients were randomly assigned 2:1 to receive either olaparib or the physician’s choice of enzalutamide or abiraterone. In cohort A, 162 patients received olaparib and 83 patients were assigned to control therapy. In cohort B, 94 patients received olaparib while 48 patients were in the control arm.
In the subgroup analysis of patients with BRCA1/2 mutations, the median overall survival (OS) was 20.1 months with olaparib versus 14.4 months with abiraterone or enzalutamide. The median radiographic progression-free survival (rPFS) was 9.8 versus 3 months, respectively.
In the previously reported primary study analysis, the median OS was superior with olaparib compared with control therapy in cohort A (19.1 months vs 14.7 months; HR, 0.69; P = .02) and cohort B (14.1 months vs 11.5 months; HR, 0.96).2 Also of note, in cohort A the median PFS was 7.4 months with olaparib compared with 3.6 months in the control arm (HR, 0.34; P <.001).
Regarding safety, adverse reactions across all grades occurring in at least 10% of patients receiving olaparib included anemia (46% vs 15% with abiraterone/enzalutamide), nausea (41% vs 19%, respectively), fatigue (41% vs 32%), decreased appetite (30% vs 18%), diarrhea (21% vs 7%), vomiting (18% vs 12%), thrombocytopenia (12% vs 3%), cough (11% vs 2%) and dyspnea (10% vs 3%). Eighteen percent of patients receiving olaparib discontinued treatment due to adverse reactions.
In the United States, the FDA approved olaparib in May 2020 for the treatment of adult patients with deleterious or suspected deleterious germline or somatic HRR gene-mutated metastatic mCRPC who have progressed following prior treatment with enzalutamide or abiraterone.
1. LYNPARZA® (olaparib) Approved in China for the Treatment of Certain Patients with BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer. Published online June 24, 2021. Accessed June 24, 2021. https://bit.ly/3dcxtDN.
2. Hussain M, Mateo J, Fizazi K, et al. Survival with olaparib in metastatic castration-resistant prostate cancer [published online September 20, 2020]. N Engl J Med. doi:10.1056/NEJMoa2022485