Niraparib for the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Abstract

Objective: To review the efficacy and safety of niraparib for the treatment of recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer (OC, FTC, and PPC). Data Sources: A literature search via MEDLINE through PubMed from August 2013 to January 2020 was performed using the key terms niraparib, PARP inhibitors, ovarian cancer, fallopian tube cancer, and primary peritoneal cancer. Study Selection and Data Extraction: Completed and ongoing trials were identified through a review of the website trial registry https://www.clinicaltrials.gov . Data Synthesis: In a phase III, double-blind clinical trial, progression-free survival improved in patients treated with niraparib compared with placebo as maintenance treatment for patients with platinum-sensitive, recurrent OC: 21 versus 5.5 months in the germline breast cancer susceptibility gene ( gBRCA) cohort (hazard ratio [HR] = 0.27; 95% CI = 0.17 to 0.41; P < 0.001) and 9.3 versus 3.9 months in the overall nongermline breast cancer susceptibility gene (non- gBRCA) cohort (HR = 0.45; 95% CI = 0.34 to 0.61; P < 0.001). Adverse events included thrombocytopenia and anemia. Relevance to Patient Care and Clinical Practice: Poly (ADP-ribose) polymerase (PARP) inhibitors have gained a place in the therapeutic management of OC, FTC, and PPC because of their ability to suppress growth of homologous recombination deficiency–positive tumors, including those with BRCA1/2 mutations. Niraparib inhibits the DNA repair mechanism vital to the survival of cancer cells, poly-ADP ribose polymerase. Conclusions: PARP inhibitors can be used as a single agent for maintenance therapy for platinum-sensitive recurrent disease in patients with partial or complete response following 2 or more rounds of platinum-based therapy.

Immune Modeling Analysis Reveals Immunologic Signatures Associated With Improved Outcomes in High Grade Serous Ovarian Cancer

“…To combat this chemoresistance, there has been a heavy focus on targeted therapies such as anti-angiogenic and poly (ADP-ribose) polymerase (PARP) inhibitors, which have shown promising results when used for maintenance or recurrent disease therapy. However, significant challenges still exist in producing long-term outcomes, with prognosis for advanced stage patients remaining poor (3)(4)(5)(6)(7).…”

The Perfect Combination: Enhancing Patient Response to PD-1-Based Therapies in Epithelial Ovarian Cancer

“…While approximately 80% of patients achieve remission following initial therapy, a majority will relapse within 16–18 months, highlighting the urgent need for novel targeted therapies [ 3 ]. In recent years, advances such as the development of anti-angiogenic and poly ADP-ribose polymerase I (PARP) inhibitors have modestly improved patient progression-free survival (PFS) [ 4 , 5 , 6 , 7 ], but a demand still exists for innovative EOC therapeutics to improve long-term outcomes. As across all cancers, EOC clinical trials currently focus on immunotherapy, with a strong emphasis placed on the most well-known immune-target, programmed cell death 1 (PD-1).…”

Exploration of N‐(6‐Indazolyl) benzenesulfonamide Derivatives as Potential Antioxidants and Antimicrobial Agents: Integrating Synthesis, In Silico Docking, and Bioactivity Profiling

“…For instance, Niraparib (marketed preparation bearing indazole nucleus) has been commonly used as an anticancer medication to treat recurrent epithelial ovarian, breast, primary peritoneal or fallopian tube, and prostate cancer. [33] The two commercially available anti-inflammatory drugs Bendazac and Benzydamine contain the 1Hindazole scaffold. [34] Granisetron, an indazole tropisetron analog, was favored by the FDA in 1997 for nausea due to cancer chemotherapy.…”

“…There is a list of miscellaneous compounds that contain indazole nuclei loaded with different functional groups showing major pharmacological properties in drug molecules and serving as a structural moiety. For instance, Niraparib (marketed preparation bearing indazole nucleus) has been commonly used as an anticancer medication to treat recurrent epithelial ovarian, breast, primary peritoneal or fallopian tube, and prostate cancer [33] . The two commercially available anti‐inflammatory drugs Bendazac and Benzydamine contain the 1 H ‐indazole scaffold [34] .…”