Report on Niraparib (Zejula®): A Comprehensive Oncological Drug Monograph

Executive Summary

Niraparib, marketed under the brand name Zejula®, is an orally bioavailable, once-daily small-molecule inhibitor of Poly (ADP-ribose) Polymerase (PARP) enzymes, specifically PARP-1 and PARP-2.[1] As a targeted therapy, its primary mechanism of action leverages the principle of synthetic lethality, proving most effective in tumors characterized by Homologous Recombination Deficiency (HRD), a state that includes, but is not limited to, germline or somatic mutations in the

BRCA1 and BRCA2 genes.[4] Niraparib has established a significant role in gynecologic oncology, primarily as a maintenance therapy for adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer following a response to platinum-based chemotherapy, in both the first-line and recurrent settings.[6]

The clinical development of Niraparib is defined by a compelling yet complex narrative. Pivotal clinical trials, most notably the PRIMA and NOVA studies, have consistently demonstrated a statistically significant and clinically meaningful benefit in Progression-Free Survival (PFS).[8] This robust effect on delaying disease progression formed the basis for its initial broad regulatory approvals. However, this efficacy is juxtaposed with a notable toxicity profile, dominated by hematologic adverse events such as thrombocytopenia, anemia, and neutropenia. This safety challenge prompted a paradigm shift in its administration, leading to the development and implementation of an individualized starting dose (ISD) based on patient weight and baseline platelet count to improve tolerability.[11]