The Status of Poly(Adenosine Diphosphate-Ribose) Polymerase (PARP) Inhibitors in Ovarian Cancer, Part 1: Olaparib

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The Status of Poly(Adenosine Diphosphate-Ribose) Polymerase (PARP) Inhibitors in Ovarian Cancer, Part 1: Olaparib
 Clinical Advances in Hematology & Oncology
Volume 14, Issue 8, August 2016


Conclusions and Future Directions
The introduction of olaparib and other PARP inhibitors represents one of the most promising genotype-directed therapies, which are destined to change the management of BRCA-associated ovarian cancer. However, a number of challenges still remain.
Firstly, it is uncertain how olaparib should be incorporated into the clinical management of both BRCA1/2-associated and sporadic ovarian cancers. It has yet to be established whether olaparib should be introduced before or after platinum therapy, in the first-line or relapsed setting, or as maintenance therapy. Secondly, it is not clear whether, as maintenance therapy, additional benefit would be obtained if olaparib (or indeed, another PARP inhibitor) maintenance were to be reinstituted at each chemotherapy-induced remission. Another challenge is determining whether combination therapy is superior to single-agent olaparib use. Owing to overlapping toxicities, particularly myelosuppression, work is required to define the optimal schedules for the combination of chemotherapy and olaparib. Furthermore, it is unclear where combination treatment with vascular endothelial growth factor and other signaling inhibitors is best employed. In addition, the role of olaparib in platinum-resistant disease requires clarity. Finally, it is not yet known whether clinical differences exist between PARP inhibitors in terms of efficacy and toxicity, or indeed whether there is a role for rechallenge with a different PARP inhibitor following progression on another.
Several phase 3 trials are underway to address many of the above questions, and it is hoped that the use of olaparib and other PARP inhibitors can be optimized to maximize PFS—and ultimately, OS—for patients with ovarian cancer.