Dr. Crane on the ongoing investigation of PARP inhibitor combinations in ovarian cancer

Erin Crane, MD, MPH, associate professor, Division of Gynecologic Oncology, Atrium Health Levine Cancer Institute, discusses the evolving role of PARP inhibition in ovarian cancer and ongoing studies specifically examining the combination of PARP inhibitors in combination with other investigational agents in the first-line setting. These studies promise to elucidate potential synergistic effects and effectiveness in this context.

Research in ovarian cancer is focused on developing a synergistic effect when combining PARP inhibitors with other agents, Crane begins. For example, the phase 3 PAOLA-1 trial showed a significant progression-free survival benefit from adding olaparib (Lynparza) to bevacizumab (Avastin) as first-line maintenance therapy, she explains. This benefit was notable in patients with homologous recombination deficiency (HRD) tumors, even in those without BRCA Mutations.

There is also an unmet need for tailored therapeutic strategies to treat patients with HRD-negative tumors, Crane continues.

Crane highlights the clinical challenges posed by homologous recombination competent (HRP) tumors, which typically exhibit prior platinum resistance and have poorer prognoses compared to patients with HRD-positive to HRD-positive tumors, Crane explains. Accordingly, it remains essential to develop therapeutic strategies tailored to this patient cohort.

Crane says studies investigating maintenance therapies and investigational agents for HRD-negative P tumors are underway, with the goal of improving treatment options and outcomes for this subgroup. Crane underscores the need for such efforts. These research efforts are necessary to extend survival outcomes and improve the clinical course of patients with HRD-negative disease, thereby extending survival and improving overall prognoses within this subgroup.

Regarding the long-term efficacy of PARP inhibitors, Crane emphasizes, adding that the sustained benefit observed with these agents is consistent with previous expectations. In particular, the observed sustained efficacy highlights the therapeutic importance of PARP inhibitors in the clinical landscape. Data collected over the past five years demonstrate the significant impact of PARP inhibitors on the ovarian cancer treatment paradigm, surpassing previous therapy modalities as the standard of care, she says.

Crane adds that early testing for germline and somatic mutations can improve identification of candidates for PARP maintenance therapy. This personalized approach facilitates timely initiation of appropriate therapies, thereby optimizing patient outcomes and treatment effectiveness. This emphasis on genetic testing also underscores the evolving paradigm of precision medicine in ovarian cancer, according to Crane.

Crane highlights the ongoing research landscape surrounding PARP inhibitors and their combination with investigational drugs.

Overall, these efforts aim to refine treatment strategies for patients with HRD-negative P tumors while exploring ways to maximize the upfront therapeutic benefit of PARP inhibitors, concludes Crane. The central role of genetic testing in treatment decision-making is highlighted and the evolving landscape of precision oncology is highlighted.