Written by: Katie Carter, PharmD, BCPS, Indiana University Health
Description: Olaparib is a poly ADP-ribose polymerase (PARP) enzyme inhibitor and is FDA approved as a targeted therapy for BRCA-mutated breast cancer, ovarian, pancreatic cancer, as well as prostate cancer. This PQI will highlight its place in therapy in these disease states, safety profiles, and clinical pearls regarding dose adjustment.
Background: Breast Cancer – About 5-10% of breast cancers can be associated with gene mutations inherited from a parent, most common mutations in the BRCA1 and BRCA2 genes.12
|Lifetime Risk of Developing Breast Cancer|
|BRCA1||Up to 72%||6.8%|
|BRCA2||69%||Less frequent cause|
Ovarian Cancer – Currently, ovarian cancer is primarily treated with surgery and systemic chemotherapy. About 25% of ovarian cancer cases are related to a BRCA mutation (15% germline and 7% somatic).14,15
Pancreatic Cancer – Up to 7% of patients with pancreatic cancer have a gBRCA mutation.16,17
Prostate Cancer – Olaparib approved in May 2020 for patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer in combination with gonadotropin-releasing hormone analog or prior bilateral orchiectomy (full indication list in supplemental information).7
- Verify the dosage form is correct
- Olaparib was previously available as both a tablet and a capsule, and the two dosage forms had different bioavailability and therefore were not interchangeable on a milligram-per-milligram basis
- Capsules were discontinued August 2018 and only the tablets are currently available
- Olaparib is available as 100 mg and 150 mg tablets
- Verify the dose is correct
- Typical starting dose for all FDA-approved indications: 300 mg orally twice daily
- See Supplemental Information Section for current FDA-approved indications
- The dose of olaparib must be adjusted to 200 mg twice daily for renal dysfunction when creatinine clearance is <50 mL/minute. Olaparib has not been studied in patients with creatinine clearance < 30 mL/minute
- Dose adjustments for adverse reactions
- Consider holding treatment or dose reductions if patients experience adverse reactions
|Dose reduction||Recommended Dose||How to Supply|
|1st dose reduction||250 mg BID||One 150 mg tablet + one 100 mg tablet BID|
|2nd dose reduction||200 mg BID||Two 100 mg tablets BID|
- Drug interactions
- Avoid concomitant use with moderate and/or strong CYP3A4 inhibitors
- If a strong CYP3A4 inhibitor must be used concomitantly, the olaparib dose should be reduced to 100 mg twice daily
- If a moderate CYP3A4 inhibitor must be used concomitantly, the olaparib dose should be reduced to 150 mg twice daily
- Avoid concomitant strong CYP3A inducers; if a moderate CYP3A inducer must be used, there is the potential for reduced efficacy of olaparib
- Laboratory monitoring
- Complete blood counts should be performed at baseline and monthly thereafter
- Renal function should be verified at baseline and periodically thereafter
- Taking other anticancer agents may cause a potentiation/prolongation of myelosuppression
Patient Centered Activities:
- Provide Oral Chemotherapy Education (OCE) sheet
- Counsel patient on side effect profile (see supplemental information)
- Instruct patient to avoid grapefruit, grapefruit juice, Seville oranges, and/or Seville orange juice
- Commercially insurance patients who qualify can enroll in a $0 copay card assistance program through AstraZeneca’s Access 360 program
- Birrer, M. Ask an expert: how do PARP inhibitors work? Cancer Updates, Research & Education. Published March 27, 2018.
- Domchek SM, Aghajanian C, Shapira-Frommer R, et al. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol. 2016;140(2):199-203.
- How common are BRCA mutations? INSIGHT from Dana-Farber Cancer Institute. Updated March 1, 2018. Available at: https://blog.dana-farber.org/insight/2018/03/brca-mutations-common.
- How do PARP inhibitors work in cancer? INSIGHT from Dana-Farber Cancer Institute. July 2016. Available at: https://blod.dana-farber.org/insight/2016/07/how-do-parp-inhibitors-work-in-cancer.
- Key statistics for ovarian cancer. American Cancer Society. Last updated January 8, 2019. Accessed April 8, 2019. Available at: https://www.cancer.org/cancer/ovarian-cancer/ about/key-statistics.html.
- Lexicomp Online, Hudson, Ohio: Lexi-Comp, Inc.; updated 2/22/19; accessed 2/25/19.
- LYNPARZA® (olaparib) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
- Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med2018; 379:2495-2505.
- NCCN Clinical Practice Guidelines in Oncology. Ovarian Cancer including Fallopian Tube Cancer and Primary Peritoneal Cancer. Version 2.2018. Available at: https://www.nccn.org/professionals/physician_gls/default.aspx#ovarian.
- Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2mutation (SOLO2/ENGOT-Ov21): a double-blind, randomized, placebo-controlled, phase 3 trial. Lancet Oncology; 2017:18(9):1274-1284.
- Robson M, Im A, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCAmutation (OlympiAD trial). N Engl J Med. 2017; 377:523-533.
- S. Breast Cancer Statistics. Breastcancer.org. Last updated Feb 13,2019. Accessed Mar 19, 2019. Available at: www.breastcancer.org/symptoms/understand_bc/statistics.
- Konstantinopoulos et al. Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer. J Clin Oncol
- Pal T et al. Cancer. 2005;104(12):2807-2816.
- Pennington KP et al. Clin Cancer Res. 2014;20(3):764-775.
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma. V.1.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed March 20, 2020.
- SEER Cancer Stat Fact Sheets: Pancreatic Cancer. National Cancer Institute website. https://seer.cancer.gov/statfacts/html/pancreas.html. Accessed March 20, 2020.
Current FDA-approved indications: (Starting dose is 300 mg twice daily for all indications)
|First-line maintenance treatment for deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer for patients who are in a complete or partial response to first-line platinum-based chemotherapy (SOLO-1 trial)|
|In combination with bevacizumab for maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer for patients who are in a complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:|
|Maintenance treatment for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer for patients who are in a complete or partial response to platinum-based chemotherapy – 2 randomized trails completed10|
OS: olaparib 29.8 months vs placebo 27.8 months (p-value 0.73)PFS (p-value <0.0001): olaparib vs placebo: 19.1 months vs 5.5 months
|Deleterious or suspected deleterious gBRCAm advanced ovarian cancer after > 3 prior lines of chemotherapy||Single arm trial PFS results:|
|Deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer after treatment with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting (OlympiAD trial)|
|Maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen (POLO trial)|
|Treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone (PROfound trial)|
PFS – progression free survival; AEs – adverse events; ORR – objective response rates; DoR – duration of response
Based on current February 2020 ASCO Guidelines13:
- Women diagnosed with epithelial ovarian cancer
- Offer germline genetic testing for BRCA1/2 and other ovarian cancer susceptibility genes at time of diagnoses
- Preform somatic tumor testing for BRCA1/2 and other likely pathogenic variants in women who are negative for a germline mutation
- First/second-degree blood relatives with a known germline susceptible gene mutation/variant should be offered individualized genetic risk evaluation/counseling and genetic testing
- Genetic evaluations can be conducted in conjunction with health care professionals including genetic counselors