An analysis of RCTs using PARP inhibitors in the treatment of breast cancer

Introduction

Breast cancer is one of the most prevalent malignancies worldwide, especially among women, as a leading cause of high mortality. Poly (ADP-ribose) polymerases (PARP) inhibitors work via synthetic lethality and PARP1 trapping by targeting DNA repair pathways within the tumor cells, primarily the PARP enzymes, which are involved in base excision repair of single-stranded breaks in the DNA. Clinical evidence suggests that they are particularly efficient among homologous recombination repair-deficient cells, which are seen in BRCA mutated tumors.

Methods

A comprehensive analysis conducted in the Pubmed database included studies published between 2021 and 2026, with the inclusion of the keywords ‘PARP inhibitor’ and ‘Breast cancer’, yielding 829 studies. Exclusion criteria were non-English language articles, reviews and animal studies. A total of 10 randomized control trials (RCTs) were evaluated in this study.

Results

The median progression-free survival was much higher for the fuzuloparib monotherapy arm than fuzuloparib-apatinib combination arm, indicating better efficacy in the treatment group over the standard chemotherapy group. The scheduled gap (48hrs) research arm receiving carboplatin combined with olaparib and chemotherapy showed better event-free survival and overall survival rates in gBRCA patients. Three-year distant disease-free survival rates and progression-free survival rates were also substantially higher for the olaparib group in comparison to the placebo group. However, this enhanced tumor lysing property is accompanied by the caveat of undesirable adverse effects including normal tissue cytotoxicity in HRR proficient cells. Thrombocytopenia has been noted following niraparib use, while marked photosensitivity was observed in the case of rucaparib.

Conclusion

The chief effectiveness of PARP inhibitors is acting against BRCA-mutated tumors. Their efficacy in managing ovarian cancers is well documented; however, translating it to the domain of breast cancers is challenged by drug resistance via homologous repair (HR) reactivation, GI disturbances, anemia, and neutropenia among others and is still a subject of ongoing research.