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, as well as ongoing trials investigating combining PARP inhibitors in combination with other investigational drugs agents, notably in the first-line setting.. These trials hold promise for elucidating potential synergistic effects and efficacy in this context.

Research in ovarian cancer is focused on develop 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 with the addition of olaparib (Lynparza) to bevacizumab (Avastin) as first-line maintenance therapy, she details. This benefit was notable in patients with homologous recombination deficient (HRD) tumors, including those without BRCA mutations.

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

Crane highlights the clinical challengeatients posed by homologous recombinationproficient (HRP) tumors, which typically exhibit earlier platinum resistance and have poorer prognoses compared with patients displaying HRD-positiveto HRD-positive tumors, Craneexplains. Accordingly, addressing therapeutic strategies tailored to this patient cohort remains imperative.

Trials investigating maintenance therapies and investigational drugs targeting HRD-negativeP tumors are underway, Crane says, aiming to enhance treatment options and outcomes for this subgroup. Crane underscores the necessity of such endeavors toThese research efforts are necessary to improve prolong survival outcomes and improve the clinical trajectory of patients with HRD-negative disease, thereby prolonging survival and augmenting overall prognoses within this subgroup.

Regarding the long-term efficacy of PARP inhibitors have demonstrated long-term efficacy, Crane emphasizes, adding that the their sustained benefits observed with these agents are, consistent with prior expectations. Notably, the enduring efficacy observed underscores the therapeutic significance of PARP inhibitors in the clinical landscape. The accrued dataData accrued over the past 5five years substantiate indicates the substantial impact of PARP inhibitors on the treatment paradigm in ovarian cancer, surpassing supplanting previous therapeutic modalities as a standard of care, she states.

Early testing for germline and somatic mutations to can improve the identificationy candidates for PARP maintenance therapy, is advocated by Crane adds. This personalized approach facilitates the timely initiation of appropriate therapies, optimizing patient outcomes and treatment efficacy. This emphasis on genetic testing also underscores the evolving paradigm of precision medicine in ovarian cancer, Crane states.

Crane underscores the continuing research landscape surroundingPARP inhibitors and their combination with investigational agents.

Overall, these efforts are directed towards refining treatment strategies for patients with HRD-negativeP tumors and , alongside exploring avenues to maximize the therapeutic benefits of PARP inhibitors in the upfront setting, Crane concludes. The pivotal role of genetic testing in treatment decision-making is underscored, highlighting the evolving landscape of precision oncology.