Written by: Katie Carter, PharmD, BCPS, Indiana University Health
Olaparib (Lynparza) is a poly ADP-ribose polymerase (PARP) enzyme inhibitor and is currently FDA approved as targeted therapy for BRCA-mutated breast cancer and ovarian cancer. This PQI will highlight its place in therapy in these disease states, safety profiles, and clinical pearls regarding dose adjustment.
About 5-10% of breast cancers can be associated with gene mutations inherited from a parent, most commonly mutations in the BRCA1 and BRCA2 genes.
|Lifetime Risk of Developing Breast Cancer|
|BRCA1||Up to 72%||6.8%|
|BRCA2||69%||Less frequent cause|
Currently, ovarian cancer is primarily treated with surgery and systemic chemotherapy. About 15% of ovarian cancer cases are related to a BRCA mutation.
Up to 7% of patients with pancreatic cancer have a gBRCA mutation. 16,17
- 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 The capsules were discontinued as of 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|
PQI Process continued:
- 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.
- Avoid concomitant use with moderate and/or strong CYP3A4 inhibitors
- Laboratory monitoring
- Complete blood counts should be performed at baseline and monthly thereafter
- Renal function should be verified at baseline and periodically thereafter
Patient Centered Activities:
- Provide Oral Chemotherapy Education Sheet
- Storage: Olaparib should be stored at room temperature and protected from moisture
- Handling: though not on the NIOSH list, Olaparib is considered hazardous due to its toxicity profile. Appropriate handling should be advised.
- 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: www.MyAccess360.com
- 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/
- 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, January 2018.
- 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 2020.
- 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. To view the most recent and complete version of the guideline, go online to org.
- 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)||· PFS results (p-value <0.0001): olaparib vs placebo: NR vs 13.8 months|
· 70% lower risk of disease progression or death with olaparib than with placebo.
|· Most common AEs with olaparib: nausea, vomiting, fatigue, anemia, diarrhea|
· Serious AEs occurred in 21% of olaparib patients vs 12% of placebo patients, most commonly anemia
|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 (SOLO-2 trial)||· PFS (p-value <0.0001): olaparib vs placebo: 19.1 months vs 5.5 months||· Most common grade 1-2 AEs in both groups: nausea, fatigue, vomiting, abdominal pain, and diarrhea|
· Most common grade 3 or higher AE with olaparib: anemia
|Deleterious or suspected deleterious gBRCAm advanced ovarian cancer after > 3 prior lines of chemotherapy||Single arm trial PFS results:|
· ORR: 34%
· Median DoR: 7.9 months
|· Serious AEs reported in 30% of patients, most frequently anemia, abdominal pain, intestinal obstruction, and pleural effusion|
|Deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer after treatment with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting (OlympiAD trial)||· PFS (p-value 0.0009):|
· Olaparib vs chemotherapy: 7 months vs 4.2 months
|· Rate of grade 3 or higher AEs was lower with olaparib (36.6%) vs chemotherapy (50.5%)|
· AEs that occurred more frequently in the olaparib group: anemia, nausea, vomiting, fatigue, headache, and cough
|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|
|· PFS results (p-value 0.0035): olaparib vs. placebo: median 7.4 months vs. 3.8 months|
· ORR: 23% in olaparib arm (12% in placebo arm)
|· Most common AE at grades 3-4 for olaparib: anemia (11%)|
· All grades AE that were >30%: Fatigue (60%), Nausea (45%), Abdominal pain (34%)
· All grade Diarrhea at 29%
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
- First or second-degree blood relatives with a known germline susceptible gene mutation or variant
- Should be offered individualized genetic risk evaluation/counseling and genetic testing
- Genetic evaluations can be conducted in conjunction with HCPs including genetic counselors