What is olaparib?
Olaparib is an oral inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3.
PARP enzymes aid in normal cellular function including DNA transcription and repair. PARP inhibitors inhibit the DNA repair pathway essential for cell survival leading to tumor cell death.
What is this approved for?
Olaparib has recently been approved for maintenance therapy of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
Olaparib was approved as maintenance therapy based on the results of the SOLO2/ENGOT-Ov21 trial. In this randomized, double-blind, placebo-controlled, phase III trial, 295 eligible patients with predicted or suspected deleterious, germline breast cancer susceptibility gene (BRCA)1/2 mutation with relapsed, high-grade serous ovarian or endometrial, primary peritoneal or fallopian tube cancer with platinum-sensitive disease who had received at least two prior lines of therapy and were in an objective response (complete or partial) were enrolled and randomized (2:1) within 8 weeks of the last dose of chemotherapy to olaparib 300 mg twice daily or placebo until disease progression. Platinum-sensitive disease was defined as disease progression occurring at least 6 months after the last dose of platinum therapy.
The primary endpoint was progression-free survival (PFS). Median PFS was significantly longer with olaparib at 19.1 months versus 5.5 months with placebo (HR 0.30, p<0.0001). Data for the secondary endpoint of overall survival was immature at time of publication, but no difference was noted (Lancet Oncol 2017;18:1274-1284).
How do you administer this drug?
Olaparib is administered as two 150 mg tablets (300 mg) by mouth twice daily for a total daily dose of 600 mg. It may be taken with or without food about 12 hours apart.
Are there any premedications needed?
While none are required, if patients have nausea or vomiting, an oral anti-nausea medication may be necessary prior to the dose or consider administration with food.
What are common side effects (> or =10%)?
* Hematologic: anemia, neutropenia, thrombocytopenia, leukopenia
* GI: nausea/vomiting, diarrhea, decreased appetite, dyspepsia, dysgeusia, stomatitis
* Infection: nasopharyngitis, sinusitis, rhinitis, influenza, upper respiratory tract infections
* Musculoskeletal: arthralgia
* Neurology: headache, pyrexia, dizziness, fatigue
* Laboratory: increased serum creatinine
What are uncommon side effects (< 10%)?
Although rare, 1 percent of patients who have taken olaparib, have developed myelodysplastic syndrome or acute myeloid leukemia. Additionally, olaparib has been associated with pneumonitis and embryo-fetal toxicity. Other side effects include hypertension, venous thrombosis, hot flashes, anxiety, and depression.
Are there any important drug interactions?
Olaparib is primarily metabolized by CYP3A4/5 enzymes. While avoidance is advised, if administration with a strong CYP3A4 inhibitor is unavoidable, the dose of olaparib should be decreased to 100 mg twice daily, or with a moderate inhibitor, 150 mg twice daily.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
There are no known hepatic dose adjustments for olaparib. Patients with moderate renal impairment, creatinine clearance 31-50 mL/minute, should receive a reduced dose of olaparib, 200 mg twice daily. Olaparib has not been studied in patients with severe hepatic or renal impairment including end-stage renal disease (less than 30 mL/minute).
Practical tips
If dose reduction is required, olaparib should be decreased to 250 mg (one 150 mg and one 100 mg tablet) twice daily. Further dose reductions should be 200 mg (two 100 mg tablets) twice daily.
What should my patients know about olaparib?
Patients should contact their health care provider if they experience any of the following:
* Shortness of breath/difficulty breathing
* Unusual bruising/bleeding
* Fevers
* Avoid grapefruit and Seville oranges
* Uncontrollable nausea/vomiting
What else should I know about olaparib?
Olaparib shouldn't be started until patients have recovered from previous hematologic toxicity with prior chemotherapy (<= Grade 1). Baseline blood counts should be obtained and then monitored monthly. For prolonged hematological toxicities, interrupt therapy and monitor weekly until recovery. If toxicity doesn't resolve to <= grade 1 after 4 weeks, refer to a hematologist.
Olaparib can cause fetal harm. Females of reproductive potential should use effective contraception during treatment and for 6 months following last dose of olaparib.
What useful links are available?
* https://www.lynparza.com
* https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208558s001lbl.pdf
Any ongoing clinical trials related to olaparib?
Clinical trials with olaparib are ongoing in several settings including as a single agent in pancreatic, urothelial, and prostate cancer, as well as in combination with radiation for head/neck cancer, with durvalumab for urothelial cancer, and with cisplatin for non-small cell lung cancer. More information is available at https://clinicaltrials.gov.
KENDALL C. SHULTES, PHARMD, is Assistant Professor, Belmont University College of Pharmacy, Hematology/Oncology Clinical Pharmacist, Vanderbilt Ingram Cancer Center Cool Springs, Nashville, Tenn. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor. SARA K. BUTLER, PHARMD, BCPS, BCOP, is Clinical Oncology Pharmacy Supervisor, Barnes-Jewish Hospital, St. Louis, Mo., and serves as a Pharmacy Forum column co-editor. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St. Louis, Mo., and serves as a Pharmacy Forum column co-editor.