Jill Alldredge, MD, assistant professor, Ob/Gyn-Gynecologic Oncology, University of Colorado (UC) Hospital Gynecologic Oncology, UC Health Cancer Center-Highlands Ranch, Denver Health Medical Center, discusses the toxicities associated with PARP inhibition and the management of those adverse effects (AEs) in patients with ovarian cancer.

Although the indications for PARP inhibitors in the treatment of ovarian are rapidly changing, they remain a key component of clinical practice, Alldredge says. Dose delays or modifications constitute a significant portion of the management of toxicity associated with PARP inhibitors, and the different PARP inhibitors feature a stepwise reduction process for practitioners to follow, Alldredge adds. Using these tools and management guidelines can assist in the management of these toxicities and allow patients to receive the higher doses of a PARP inhibitor for a longer duration of time.

AEs commonly associated with PARP inhibition in patients with ovarian cancer include gastrointestinal and hematologic toxicities, as well as fatigue. Although the rates of these AES vary between the different PARP inhibitors, the onset of toxicities generally occurs approximately one month into treatment, in the range of 30 to 45 days, Alldredge notes.

Regarding hematologic toxicities, niraparib (Zejula), for example, can be redose based on a patient’s weight or platelet counts; otherwise, dose holds and reductions can be made when a patient’s platelet count is under 100 x 109 L, Alldredge says. Platelet transfusions are rarely performed in patients receiving PARP inhibitors, unless they are experiencing active bleeding or a platelet count under 10 x 109 L, Alldredge says. For patients experiencing PARP-induced anemia, a red blood cell transfusion may be utilized based on symptoms, and due to the mechanism of this anemia, iron supplements are not very effective in this setting, Alldredge notes. Moreover, neutropenia is managed with dose delays and reductions.

Although nausea is also a common AE, ways to mitigate this include evening dosing, small meals prior to dosing, and treatment with ondansetron. Fatigue is one of the most common AEs associated with PARP inhibitors, and this can be managed by advising patients on good habits regarding sleep and hygiene, as well as screening for depression and addressing any underlying issues, Alldredge concludes.

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Jill Alldredge, MD, discusses the toxicities associated with PARP inhibition and the management of those adverse effects in patients with ovarian cancer.

Dr. Alldredge on Managing AEs With PARP Inhibitors in Ovarian Cancer

Jill Alldredge, MD, assistant professor, Ob/Gyn-Gynecologic Oncology, University of Colorado (UC) Hospital Gynecologic Oncology, UC Health Cancer Center- Highlands Ranch, Denver Health Medical Center, discusses the management of symptoms in patients with ovarian cancer during treatment with a PARP inhibitor.

A multimodal approach is needed to address the management of symptoms in patients with ovarian cancer , whether those symptoms stem from the disease, treatment with chemotherapy, or treatment with a PARP inhibitor, Alldredge says. Given that patients with ovarian cancer are already receiving daily medication, managing symptoms without administering additional medicine can be beneficial.

Symptom management outside of additional medication can include physical therapy, fitness programs, survivorship groups, support groups, massage therapy, acupuncture, and pharmacotherapeutic prophylaxis. However, there are not many data-driven approaches for hematologic recovery after PARP inhibitors; therefore, the management of energy, fatigue, and nausea can be done through multimodal strategies, Alldredge explains.

Since dose reductions are common for patients treated with PARP inhibitors, optimal treatment strategies can be developed as more experience is gained from their use, Alldredge explains. For example, starting patients at lower doses and ramping them up could allow for the mitigation of toxicity while maintaining outcomes.

New data may also shed light on alternative strategies to support hematologic recovery or affect the duration of treatment, Alldredge adds, noting additional research could show that patients may not need to receive PARP inhibitor maintenance for 2 to 3 years.

There are several maintenance strategies where the indications are under review, and the current duration of those strategies is indefinite, with patients continuing PARP inhibitor maintenance in the recurrent setting until they experienced unacceptable toxicity or disease progression, Alldredge says. Further data to guide the duration of treatment with PARP inhibitor maintenance will help improve toxicities and potentially lower the risk for patients to develop myelodysplastic syndromes, Alldredge concludes.

Jill Alldredge, MD, discusses the management of symptoms in patients with ovarian cancer during treatment with a PARP inhibitor.

Jill Alldredge, MD

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Dr. Alldredge on Managing AEs With PARP Inhibitors in Ovarian Cancer

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