Exploring and comparing adverse events between PARP inhibitors

Christopher J LaFargue, Graziela Z Dal Molin, Anil K Sood, Robert L Coleman, Christopher J LaFargue, Graziela Z Dal Molin, Anil K Sood, Robert L Coleman

Abstract

Ovarian cancer remains one of the most challenging malignancies to treat. Targeted therapies such as poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as one of the most exciting new treatments for ovarian cancer, particularly in women with BRCA1 or BRCA2 mutations or those without a functional homologous recombination repair pathway. Perhaps the most advantageous characteristic of PARP inhibitors is their mechanism of action, which targets cancer cells on the basis of their inherent deficiencies while seemingly avoiding normally functioning cells. Although health-care providers might assume a low toxicity profile because of their specific mechanism of action, PARP inhibitors are not completely benign and overall show a class effect adverse-event profile. Further complicating this situation, three different PARP inhibitors have been approved by the US Food and Drug Administration since 2014, each with their own specific indications and individual toxicity profiles. The diversity of adverse events seen both within and across this class of drug underscores the importance of having a comprehensive reference to help guide clinical decision making when treating patients. This Review characterises and compares all toxicities associated with each PARP inhibitor, both in monotherapy and in novel combinations with other drugs, with a particular focus on potential management strategies to help mitigate toxic effects. Although the excitement surrounding PARP inhibitors might certainly be warranted, a thorough understanding of all associated toxicities is imperative to ensure that patients can achieve maximal clinical benefit.

Conflict of interest statement

Declaration of interests

RLC reports personal fees from Cell Medica, DelMar Pharmaceuticals, Geistlich, Genmab, ImmunoGen, Perthera, Takeda, Tesaro, TRM Oncology, Clovis, Aravive Biologics Inc, ArQule, AstraZeneca, Bayer, Caris Life Sciences, Eisai·Morphotek, Gamamabs, Janssen, Medscape, Merck, Myriad, and Roche, outside the submitted work; and grants from Clovis, AstraZeneca, Janssen, Merck, and Roche, outside the submitted work. AKS is part of the advisory board of Kiyatec, is a stockholder for Biopath, a consultant at Tesaro, and reports grants from M-Trap, all outside the submitted work. The remaining authors declare no competing interests.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Figures

Figure 1:. Treatment paradigm for the use…
Figure 1:. Treatment paradigm for the use of poly (ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer
Olaparib, rucaparib, and niraparib are approved by the US Food and Drug Administrat ion for use in ovarian cancer as a maintenance therapy in the platinum-sensitive recurrent setting. Rucaparib and olaparib are approved for recurrent disease. First-line and first-recurrence therapies are under investigation. FDA=Food and Drug Administration. gBRCA=germline BRCA mutation. M=maintenance. sBRCA=somatic BRCA mutation.

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