Brand: Lynparza

Initial US Approval

  • 2014. Prostate indications added May 19, 2020 (HRR gene-mutated mCRPC, monotherapy) and May 31, 2023 (BRCA-mutated mCRPC, with abiraterone).1,6

Indications

HRR Gene-Mutated Metastatic Castration-Resistant Prostate Cancer (Monotherapy):

  • Adult patients with deleterious or suspected deleterious germline or somatic HRR gene-mutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone. Select patients based on an FDA-approved companion diagnostic.1

BRCA-Mutated mCRPC (With Abiraterone):

  • In combination with abiraterone and prednisone or prednisolone for adult patients with deleterious or suspected deleterious BRCA-mutated mCRPC. Select patients based on an FDA-approved companion diagnostic.1
  • Patient selection: monotherapy, FoundationOne CDx (tumor; 14 HRR genes), BRACAnalysis CDx (blood; germline BRCA1/2), or FoundationOne Liquid CDx (plasma; ATM, BRCA1, BRCA2); combination, BRCA1/2 in tumor, blood, or plasma. PPP2R2A, a PROfound cohort B gene, is excluded because of an unfavorable risk-benefit profile.1,7

Recommended Dose/Route

  • 300 mg orally twice daily, with or without food, until disease progression or unacceptable toxicity.1
  • With abiraterone: abiraterone 1000 mg orally once daily plus prednisone or prednisolone 5 mg orally twice daily.1
  • Patients should also receive a GnRH analog concurrently or should have had bilateral orchiectomy.1

Dose Reductions for Adverse Reactions

Figure

Pivotal Study

PROfound (NCT02987543)

  • Key Inclusion Criteria: mCRPC progressing on prior enzalutamide or abiraterone with a tumor alteration in 1 of 15 HRR genes by central tissue testing; cohort A, BRCA1, BRCA2, or ATM; cohort B, 12 other HRR genes.1,2
  • Treatment: randomized 2:1, open label, to olaparib 300 mg twice daily (n=256) or investigator's choice of enzalutamide or abiraterone (n=131); cohort A, 162 vs 83.1

PROpel (NCT03732820)

  • Key Inclusion Criteria: first-line mCRPC, unselected for HRR status; prior abiraterone excluded; prior docetaxel for hormone-sensitive disease allowed. BRCA status was determined after randomization (85 of 796 patients, 11%).1,4
  • Treatment: randomized 1:1, double blind, to olaparib plus abiraterone (n=399) or placebo plus abiraterone (n=397), each with prednisone or prednisolone.1
Figure
  • Fair balance: in PROfound, 66% of control patients crossed over to olaparib. In PROpel, BRCA status was not a stratification factor and the subgroup analysis was not controlled for type I error; final ITT OS was not statistically significant (42.1 vs 34.7 months; HR, 0.81; 95% CI, 0.67-1.00; P=.054).1,3,5

Safety

PROfound (N=256)

  • Summary: serious adverse reactions 36%, fatal 4%, discontinuation 18%, dose reduction 22%, dose interruption 45%; anemia was the leading cause of each.1
  • Key warnings: myelodysplastic syndrome/acute myeloid leukemia (about 1.2% across studies; fatal in 54% of cases); pneumonitis (1.0%); venous thromboembolism (8% across PROfound and PROpel, pulmonary embolism 6%); hepatotoxicity, including drug-induced liver injury; embryo-fetal toxicity (male patients should use effective contraception and not donate sperm during treatment and for 3 months after the last dose).1
Figure

PROpel (N=398)

  • Summary: serious adverse reactions 39%, fatal 6% (COVID-19, 3%), discontinuation of olaparib 16%, dose reduction 21%, dose interruption 48%.1
  • Key warnings: venous thromboembolism 8%; grade 3 or 4 anemia 16%.1
Figure

References

  1. Lynparza (olaparib) tablets. Prescribing information. AstraZeneca Pharmaceuticals LP; revised 07/2025. Accessed October 2026.
  2. de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382(22):2091-2102. doi:10.1056/NEJMoa1911440
  3. Hussain M, Mateo J, Fizazi K, et al. Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med. 2020;383(24):2345-2357. doi:10.1056/NEJMoa2022485
  4. Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid. 2022;1(9):EVIDoa2200043. doi:10.1056/EVIDoa2200043
  5. Saad F, Clarke NW, Oya M, et al. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results. Lancet Oncol. 2023;24(10):1094-1108. doi:10.1016/S1470-2045(23)00382-0
  6. FDA approves olaparib with abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer. US Food and Drug Administration. May 31, 2023.
  7. List of cleared or approved companion diagnostic devices. US Food and Drug Administration. Accessed October 2026.