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The approval was based on the PROfound trial, in which olaparib reduced the risk of death by 31% compared with abiraterone acetate or enzalutamide.
The European Commission has approved olaparib (Lynparza) for the treatment of patients with BRCA 1/2–mutation positive metastatic castration-resistant prostate cancer (mCRPC).1
The approval was supported by the phase 3 PROfound trial, in which the risk of death was reduced by 31% with olaparib compared with abiraterone acetate (Zytiga) or enzalutamide (Xtandi; HR, 0.69; P <.0001) in patients with mCRPC harboring an alteration in BRCA1, BRCA2, or ATM.2 Olaparib also reduced the risk of disease progression or death by 66% (HR, 0.34; P <.001).
“This approval in the EU is a landmark moment that begins a new era of precision medicine in prostate cancer. Lynparza now provides a targeted treatment option at a molecular level to patients with advanced prostate cancer who have historically poor prognosis and few treatment options,” Johann de Bono, MB CHB, PhD, MSC, one of the principal investigators of the PROfound trial and head of drug development at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, stated in a press release.
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.
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). 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)
Across the study, the most common adverse events among patients receiving olaparib group were anemia (39%), nausea (36%), and fatigue or asthenia (32%). Treatment with olaparib was discontinued because of anemia in 7% of patients and because of neutropenia, thrombocytopenia, nausea, vomiting, or fatigue or asthenia in 1% of the patients for each.
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 approved in the EU for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer. Accessed November 5, 2020. https://bit.ly/32iQleT. Accessed November 5, 2020.
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