PARP Inhibitors in Newly Diagnosed and Recurrent Ovarian Cancer

Abstract

Ovarian cancer is the most lethal gynecologic malignancy, characterized by a high death-to-incidence ratio. Platinum-based chemotherapy is the mainstay of treatment for newly diagnosed and platinum-sensitive recurrent ovarian cancer. Poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) have been incorporated into the treatment strategy for ovarian cancer. PARP inhibitors showed particular benefit for patients harboring defects in DNA repair pathways. Accumulating evidence showed that PARP inhibitors provide a benefit in newly diagnosed advanced ovarian cancer, even in the absence of BRCA mutation, as reported in the PRIMA, PRIME, and ATHENA-mono trials. Interestingly, the PAOLA-1 study provides another important finding, supporting the adoption of olaparib plus bevacizumab in patients with homologous recombination deficiency. Although those results are exciting, several patients develop resistance to PARP inhibitors. Hence, new combinations are under investigation to identify new treatment strategies to overcome this resistance. Currently, researchers are focused on the possibility to adopt PARP inhibitors even in the setting of platinum-resistant disease. The present critical review aims to report the current landscape and further perspective for strengthening PARP inhibitors' effectiveness in newly diagnosed and recurrent ovarian cancer.

BRCA Mutation Patients: Are There Other Predisposing Factors for Ovarian Cancer Occurrence? A Multicenter Retrospective Study

“…Thus, PARPi provides particular benefit for patients defective in DNA repair pathways. Growing evidence suggest that the adoption of PARPi allows for shifting the paradigm of care for newly diagnosed and recurrent ovarian cancer patients [28]. Emerging data suggest that PARPi may also have some activity in patients with platinum-resistant ovarian cancer.…”

PARP Inhibitors: Strategic Use and Optimal Management in Ovarian Cancer

“…Further research is required to inform the future and optimal use of PARPi with anticipation that they will find an expanded role in augmenting immunotherapy in combinations with other DNA Damage Response interacting agents. This is well reviewed by Giannini et al, but the article’s focus is on the exploration of PARPi in the setting of platinum-resistant disease, which should only be pursued in clinical trials [ 31 ].…”

Advances in nanotechnology-enabled drug delivery for combining PARP inhibitors and immunotherapy in advanced ovarian cancer

“…In a recent study by Giannini et al, significant concerns pertaining to the utilization of PARPis have been thoughtfully addressed. A notable concern highlighted is the reoccurrence of the disease in a significant number of individuals who received treatment with these inhibitors within a 30-month span after their first diagnosis [ 42 ]. There are lingering uncertainties surrounding the management of relapses, the optimal positioning of PARPis as either first-line or second-line therapies, and whether patients can be managed effectively with PARPis alone.…”

“…On the other hand, the potential of PARPis in conjunction with antiangiogenic therapy is encouraging, as is the prospect of utilizing PARPis to augment the effectiveness of ICIs. In addition, scholars are currently engaged in the investigation of methodologies aimed at addressing resistance to PARPis by targeting the cell cycle [ 42 ].…”