Changes in Olaparib Indications Demonstrate Need for Best Practices for Nurses

As the Food and Drug Administration continues to approve additional indications for olaparib (Lynparza), health care providers and caregivers should be aware of the potential adverse effects (AEs) associated with treatment.

Along with best practices for dosing and AE management, guidelines for oncology nurses about the new indications and tablet formulations of the PARP inhibitor were presented at the ONS Congress in Washington, DC on May 19.

Olaparib is currently approved for the following indications:

• Maintenance therapy for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in adult patients with complete or partial response (CR/PR) to platinum-based chemotherapy regardless of BRCA status;
• Adult patients with deleterious or suspected deleterious germline BRCA-positive, advanced ovarian cancer who received ≥3 prior lines of chemotherapy;
• Patients with deleterious or suspected deleterious germline BRCA-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who received prior chemotherapy in the neoadjuvant, adjuvant, or metastatic setting; and
• Patients with hormone receptor-positive breast treated with a prior endocrine therapy or considered inappropriate for endocrine therapy.

Because of this changing treatment landscape, it is key for nurses to understand the indication, formulation, and dosing of olaparib, an agent that demonstrates significant progression free survival in women and has a manageable toxicity profile. Additionally, olaparib has no significant detrimental effect on the patient’s quality of life, Patricia McLaughlin, RN, BSN, MSN, ARNP-C, Senior Medical Science Liaison, AstraZeneca Pharmaceuticals, said in an interview with Oncology Nursing News.

When it comes to dosing, nurses should be aware of olaparib’s 2 formulations: tablets with doses of 150 mg and 100 mg, and capsules with a dose of 50 mg. Because they are not bioequivalent, said McLaughlin, the 2 formulations cannot be substituted for each other on a milligram-to-milligram basis.

The current recommended dose is 300 mg in tablet form (1 dose of two 150 mg tablets), with a maximum permissible dose per day of 600 mg. Patients are not to exceed 4 tablets a day, and 100 mg tablets are to be used for dose reductions only.

Capsules are only indicated for patients with ovarian cancer who have received 3 or more prior lines of therapy, in which case the maximum dose per day is 800 mg. It is important to note, however, that given the higher pill burden, the capsule formulation will eventually be phased out from US markets. As for how this affects patients, “There is ongoing communication to healthcare practitioners to all prescribers regarding the phasing out of the capsule formulation,”

The authors noted that dose interruptions are permitted for up to 4 weeks following an AE. Olaparib should be discontinued for 3 or more days before planned surgery or radiation therapy, and can be reinstated after surgery and within 4 weeks of radiation therapy, once bone marrow function has fully recovered.

In the event of toxicity, dose reduction can be considered. Where the initial dose is 2 doses of 2 150 mg tablets per day (for a total daily dose of 600 mg), an initial reduction to 1 150 mg and 1 100 mg tablet per dose (for a total daily intake of 500 mg) and a final reduction to 2 100 mg tablets per dose (for a total daily intake of 400 mg) are recommended.

In addition to affecting the patient’s quality of life, McLaughlin said, knowing how to manage patients’ symptoms is integral to maintaining the effectiveness of treatment. Therefore, these best practices suggest ways that nurses can help manage the most common AEs in their patients without dose interruptions or reductions.

The authors suggested managing nausea and vomiting, the most common AE, with antiemetics. The next most common AE, fatigue, is generally mild to moderate and appears within the first 3 months of treatment. In these patients, dose interruptions or reductions are permitted if required, but the authors suggest managing symptoms through such methods as energy conservation, exercise, sleep, nutritional counseling, and caution while driving or using machinery.

Mild to moderate anemia, the third most common AE while taking olaparib, is usually treated with iron, folic acid and vitamin B12 supplements. Supportive treatments such as transfusions can also be used, along with a maximum dose interruption of 4 weeks, and dose reduction upon recovery.

The authors also mentioned that olaparib should be discontinued in patients who develop myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), pneumonitis, and embryo-fetal toxicity.

In women of child bearing potential, contraception is recommended during treatment for up to 6 months after the last dose, and lactating women should avoid breastfeeding during treatment and for a full month after their last dose.

Patients with mild to moderate liver impairment or mild kidney impairment do not need any dose adjustments, while dose reductions are recommended for those with moderate kidney impairment.

Reference:

McLaughlin P, Vanderploeg H, Munley J, Briceno J. Patients first: nursing best practices for the new formulation, dosing, and indication of olaparib. Presented at: Oncology Nursing Society 43rd Annual Congress; May 17-20, 2018; Washington, D.C. Poster-IS19. epo.epostersonline.net/ons2018/node/2470?view=true