Olaparib: The First PARP Inhibitor With 7 Indications Across 4 Tumor Types

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.