Olaparib: The First PARP Inhibitor With 7 Indications Across 4 Tumor Types
Olaparib was the first PARP inhibitor to be developed and has been the most studied.
Olaparib (Lynparza) is an oral poly (ADP-ribose) polymerase (PARP) inhibitor. PARP enzymes are responsible for repairing single-strand DNA breaks.1 Enzyme inhibition results in double-strand DNA breaks normally repaired by homologous recombination.
However, BRCA-mutant cells are defective and this homologous recombination defect (HRD) causes double-strand DNA breaks to accumulate, resulting in cell death. Approximately 15%-21% of ovarian cancers hold BRCA mutations and half could be HRD-positive and, therefore, responsive to PARP inhibitors.1
Dosage
Olaparib is available in 100 mg and 150 mg tablets and is dosed as 300 mg twice daily, with or without food.2 Treatment should be continued until disease progression, intolerability, or at the 2-year mark. Patients who experience complete response at 2 years should stop treatment unless the clinician can obtain benefit from continuous treatment.2
FDA Approval
Olaparib was the first PARP inhibitor to be developed (2005) and hence the most studied.3 It was approved by the FDA on December 19, 2018, as monotherapy for the first-line maintenance treatment of BRCA-mutated (BRCAm) advanced ovarian cancer.4
The FDA extended the approval to first-line maintenance of HRD-positive advanced ovarian cancer in combination with bevacizumab on May 8, 2020.4 Olaparib is the only PARP inhibitor approved for first-line maintenance of germline BRCAm (gBRCAm) ovarian cancer.3 Olaparib can also be used for recurrent ovarian cancers after response to platinum-based chemotherapy.2
Olaparib is also indicated for a certain type of BRCA gene, human epidermal growth factor receptor 2-negative breast cancer that has metastasized. These patients should have first received chemotherapy either before or after cancer spread.2
In addition, olaparib can be used as first-line maintenance treatment of gBRCAm metastatic pancreatic cancer and homologous recombination repair gene-mutatedmetastatic castration-resistant prostate cancer.2
Adverse Effects (AE), Management, and Monitoring
Olaparib’s most common AEs are fatigue, nausea, vomiting, and anemia.3 A 2018 study found anemia as the most common serious AE, occurring in 7% of patients in the olaparib group and zero patients in the placebo group. No AEs during or up to 30 days after this trial resulted in death.5
Clinicians should monitor patient fatigue using a 0-10 scale, with 10 being the most severe.1 Nonpharmacologic interventions include energy conversation methods such as prioritizing tasks, avoiding multitasking, and timing activities when energy is highest. Other interventions include exercise, massage therapy, and cognitive behavioral therapy.1
Occasional breaks in olaparib therapy can help fatigue return to baseline.1 The olaparib dose can be reduced to 200 mg twice daily in more severe cases. Methylphenidate can improve fatigue; however, clinicians should first rule out depression or sleep disturbances before initiation.1
Gastrointestinal upset may subside within 1 to 2 months of treatment initation.3 Antiemetics may help relieve nausea and vomiting.
Olaparib requires weekly complete blood counts with differential during the first month of treatment and once monthly thereafter. Clinicians should also obtain a complete metabolic panel at baseline and then periodically.3
Pregnancy/Lactation
Olaparib can cause fetal harm, therefore, females should use effective contraception during treatment and for 6 months after the last dose.6
Males should not donate sperm during treatment and should use effective contraception until 3 months after the last dose. Clinicians should advise lactating women not to breastfeed during treatment and for 1 month after last dose due to lack of studies and the possibility of serious AEs.6
About the Author
Sara L. Tolliday, PharmD, RPh, is a full-time clinical pharmacist in the Outpatient Pharmacy at Wentworth-Douglass Hospital in Dover, NH.
References
1. Moore KN, Monk BJ. Patient Counseling and Management of Symptoms During Olaparib Therapy for Recurrent Ovarian Cancer. Oncologist. 2016;21(8):954-963. doi:10.1634/theoncologist. 2015-0268.
2. AstraZeneca. Lynparza (olaparib) HCP site – Physician info and Resources. Last updated April 2021. Accessed October 13, 2021. www.lynparzahcp.com
3. Taylor KN, Scott M. PARP inhibitors: Choosing what to use in epithelial ovarian cancer. Contemp Ob Gyn. 2020; 65(4):30-36.
4. Arora S, Balasubramaniam S, Zhang H, et al. FDA Approval Summary: Olaparib Monotherapy or in Combination with Bevacizumab for the Maintenance Treatment of Patients with Advanced Ovarian Cancer. Oncologist. 2021;26(1):e164-e172. doi:10.1002/onco.13551
5. Moore K, Colombo N, Scambia G, et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018;379(26):2495-2505. doi:10.1056/NEJMoa1810858
6. Lynparza (olaparib) tablets [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals; March 2021.
