Clinical Data May Support PARP Inhibition in Somatic BRCA-Mutant TNBC

In a conversation with CancerNetwork®, Jade E. Jones, MD, assistant professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine and medical oncologist at the Emory Winship Cancer Institute, discussed how clinicians determine treatment selection for patients with triple-negative breast cancer (TNBC) harboring biopsy-confirmed somatic BRCA mutations.

Jones began by suggesting that data support the use of PARP inhibition for germline mutations, including in a trial she conducted that showed how treatment with olaparib (Lynparza) or talazoparib (Talzenna) was associated with an improvement in clinical outcomes for those with inherited BRCA mutations. She further explained that despite no definitive guidelines, data exist that support the use of PARP inhibition in patients with somatic mutations as well.

Furthermore, Jones explained that patients with BRCA1- or BRCA2-mutant TNBC may benefit from PARP inhibition, particularly those with hormone receptor (HR)-positive status who have progressed on prior endocrine therapy, those who are resistant to chemotherapy, or those who progressed after receiving an antibody-drug conjugate (ADC). She concluded by expressing that she tries to facilitate clinical trial enrollment for patients with BRCA-mutant TNBC to receive PARP inhibitors given data supporting its use in these patients.

Transcript

There are data for how we use PARP inhibitors for germline mutations. That was our trial where we…used olaparib or talazoparib, and showed improvement in clinical outcomes, specifically people who had inherited [BRCA2 and BRCA1] mutations. However, there are also data to support that these mutations may also respond to PARP inhibitors for people who have somatic [mutations]. Technically, it’s not written in the guidelines to use these drugs, but there are clinical trials—and I’ve sent my patients for clinical trials—where if patients have these mutations, they’re receiving PARP inhibitors.

I would say if you have a patient who has triple-negative [disease]—these data are mostly in our [patients with] triple-negative and hormone receptor–positive [disease and] BRCA1 and BRCA2 [mutations]. If they [have] hormone receptor-positive [disease], have exhausted their endocrine therapy but are still wanting an oral option, or [have] triple-negative [disease] and tend to be more chemotherapy-resistant or had an ADC, then you’re trying to get a drug that may be a bit more targeted for those patients; to consider a PARP inhibitor. If there is a clinical trial, I would try to get them on [one] where we’re using the PARP inhibitor. That’s what I would say: that there’s a role for PARP inhibitors in somatic BRCA mutations. A lot of this is being done in clinical trials, but there are data to support that there are some patients who will respond to PARP inhibitors in this case.