Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer
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LEADING ARTICLE
Movement of Poly‑ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer Michaela Onstad1 · Robert L. Coleman2 · Shannon N. Westin1
© Springer Nature Switzerland AG 2020
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.
Key Points The use of front-line PARP maintenance therapy in advanced ovarian cancer is most beneficial among patients with BRCA-associated ovarian cancers, followed by patients with HRD tumours In determining which patients should be offered frontline maintenance PARP inhibitors, there are multiple factors to consider such as FDA indication, dosing preference, toxicity, risks versus benefits for each patient population, and cost.
* Shannon N. Westin [email protected] 1
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas, M.D. Anderson Cancer Center, 1155 Herman Pressler Dr. CPB 6.3279, Houston, TX 77030, USA
US Oncology Research, The Woodlands, TX, USA
2
1 Introduction Ovarian cancer is the most lethal gynaecologic malignancy in the USA, with approximately 22,000 new cases and 14,000 cancer-related deaths each year [1]. The majority are diagnosed at an advanced stage where primary treatment with platinum-based chemotherapy and tumour reductive surgery leads to high rates of remission. Unfortunately, most women ultimately experience disease recurrence within the first 3 years of
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