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Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer

Abstract

The use of poly (ADP-ribose) polymerase (PARP) inhibitors in the front-line management of advanced ovarian cancer has recently emerged as an exciting strategy with the potential to improve outcomes for patients with advanced ovarian cancer. In this article, we review the results of four recently published Phase III randomised controlled trials evaluating the use of PARP inhibitors in the primary treatment of ovarian cancer (SOLO1, PRIMA, PAOLA-1, and VELIA). Collectively, the studies suggest that PARP maintenance in the upfront setting is most beneficial among patients with BRCA-associated ovarian cancers (hazard ratios range from 0.31 to 0.44), followed by patients with tumours that harbour homologous recombination deficiencies (hazard ratios range from 0.33 to 0.57). All three studies that included an all-comer population were able to demonstrate benefit of PARP inhibitors, regardless of biomarker status. The FDA has approved olaparib for front-line maintenance therapy among patients with BRCA-associated ovarian cancers, and niraparib for all patients, regardless of biomarker status. In determining which patients should be offered front-line maintenance PARP inhibitors, and which agent to use, there are multiple factors to consider, including FDA indication, dosing preference, toxicity, risks versus benefits for each patient population, and cost. There are ongoing studies further exploring the front-line use of PARP inhibitors, including the potential downstream effects of PARP-inhibitor resistance in the recurrent setting, combining PARP-inhibitors with other anti-angiogenic drugs, immunotherapeutic agents, and inhibitors of pathways implicated in PARP inhibitor resistance.

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Correspondence to Shannon N. Westin.

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Funding

Dr Westin is supported by NIH SPORE in Ovarian Cancer (1P50CA217685-01) and a GOG Foundation Scholar Investigator Award. The funding sources had no involvement in study design, data collection, or writing of the manuscript.

Conflict of interest

SNW is a consultant for AstraZeneca, Circulogene, Clovis Oncology, Eisai, GSK/Tesaro, Merck, Novartis, Pfizer, Roche/Genentech and Zentalis. SNW receives research support from ArQule, AstraZeneca, Bayer, Clovis, Cotinga Pharmaceuticals, Novartis, Roche/Genentech, and GSK/Tesaro. RLC is a consultant for AstraZeneca, Clovis Oncology, GSK/Tesaro, Novartis, Roche/Genentech, Eisai, Merck, Pfizer, Novocure, Genmab, Gamamab, Oncosec, Tarveda. RLC receives research funding from AbbVie, Genmab, Merck, AstraZeneca, Clovis Oncology, Roche/Genentech. MO has no conflicts of interest to disclose.

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Onstad, M., Coleman, R.L. & Westin, S.N. Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer. Drugs 80, 1525–1535 (2020). https://doi.org/10.1007/s40265-020-01382-0

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