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

“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.