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“With [PARP inhibitors], the risk of secondary malignancies is definitely something that needs to be talked about [with] patients.”

Whitney Goldsberry, MD, assistant professor, Department of Obstetrics, Gynecology, and Women’s Health, University of Louisville School of Medicine, discusses the potential risk of secondary malignancies in patients with ovarian cancer receiving PARP inhibitors.

Although PARP inhibitors have become key agents within the ovarian cancer treatment paradigm for select patients, their use is associated with the risk of developing secondary malignancies, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), that must be carefully addressed with patients, Goldsberry explains.

Results of a meta analysis of clinical trials examining PARP inhibitors across various solid tumors highlighted that the frontline use of PARP inhibitors was associated with an increased risk of secondary malignancies vs control therapies (incidence rate ratio [IRR], 5.43; 95% CI, 1.51-19.60). In the setting of recurrence, the risk of developing MDS or AML was similar between patients treated with PARP inhibitors or a control therapy (IRR, 1.00; 95% CI, 0.62-1.63).

Within the ovarian cancer space, data from the phase 3 SOLO1 (NCT01844986), PAOLA-1 (NCT02477644), and SOLO2 (NCT01874353) trials, patients treated with olaparib (Lynparza)-based therapies experienced MDS/AML at rates of 1.9%, 1.6%, and 8%, respectively. In the control arms of these studies, the respective rates of secondary malignancies were 0.8%, 2.3%, and 4%.

In the phase 3 PRIMA (NCT02655016) and NOVA (NCT01847274) trials, patients with ovarian cancer treated with niraparib (Zejula) experienced MDS/AML at rates of 1.2% and 7%, respectively. In the control arms of these studies, the respective rates of secondary malignancies were 1.2% and 3%.

These hematologic toxicities are serious and potentially fatal, emphasizing the need for vigilance during therapy, Goldsberry notes.

In addition to secondary malignancies, other hematologic adverse effects (AEs), such as thrombocytopenia and neutropenia, are commonly reported with PARP inhibitors, she says. Non-hematologic toxicities include gastrointestinal AEs such as nausea, vomiting, and diarrhea, she adds.

The serious nature of secondary malignancies requires clinicians to inform patients of these risks and closely monitor patients for these types of AEs, Goldsberry concludes.

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Whitney Goldsberry, MD, discusses the potential risk of secondary malignancies in patients with ovarian cancer receiving PARP inhibitors.

Dr Goldsberry on the Risk of Secondary Malignancies With PARP Inhibitors in Ovarian Cancer

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“I'm hesitant to put patients on any type of PARP inhibitor unless they are homologous repair–deficient or [harbor] a 

 mutation. If they do [have one of these markers], then, right now, I'm thinking olaparib is probably the best choice [among approved PARP inhibitors], given the overall survival data from [phase 3] SOLO 1 trial that's out compared with the phase 3 PRIMA trial data [for niraparib].”

Whitney Goldsberry, MD, assistant professor, Department of Obstetrics, Gynecology and Women's Health, University of Louisville School of Medicine, discusses key considerations for selecting a PARP inhibitor in the maintenance treatment of patients with ovarian cancer, noting the importance of biomarker status in guiding therapy decisions.

, are approved by the FDA in the maintenance setting for patients with advanced ovarian cancer. Both agents are approved for the maintenance treatment of adult patients with deleterious or suspecteddeleterious germline or somatic advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy; however, olaparib is indicated only for patients harboring 

 mutations, and niraparib is indicated for patients in this setting irrespective of biomarker status.

Although niraparib could be utilized in the all-comer population, Goldsberry highlights that there was a smaller progression-free survival (PFS) benefit observed in the homologous recombination–proficient (HRP) subset of patients during the phase 3 PRIMA trial (NCT02655016). Consequentially, Goldsberry expresses hesitancy in prescribing PARP inhibitors for this subgroup, given the modest benefit relative to potential toxicities.

For patients with homologous repair–proficient tumors or 

mutations, olaparib has emerged as her preferred choice, Goldsberry says. The phase 3 SOLO1 trial (NCT01844986) demonstrated significant overall survival (OS) benefits with olaparib vs placebo in patients with 

When selecting a PARP inhibitor, clinicians must balance efficacy with toxicity profiles. Both olaparib and niraparib are associated with class-specific adverse effects such as anemia, thrombocytopenia, and nausea, and individual patient tolerance and prior treatment history may influence decision-making, Goldsberry concludes.

Whitney Goldsberry, MD, discusses considerations for selecting a PARP inhibitor in the maintenance treatment of ovarian cancer.

Whitney Goldsberry, MD

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Dr Goldsberry on the Risk of Secondary Malignancies With PARP Inhibitors in Ovarian Cancer

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