Journal
LANCET ONCOLOGY
Volume 20, Issue 1, Pages E15-E28Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S1470-2045(18)30786-1
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Funding
- US National Institutes of Health [CA016672, 2T32CA101642, UH3TR000943, P50 CA217685, P50 CA083639, R35 CA209904]
- Cancer Prevention Research Institute of Texas [RP120214]
- Ovarian Cancer Research Fund Inc (Program Project Development Grant)
- Judi A Rees and Albert Pisani Ovarian Cancer Research Fund
- Blanton-Davis Ovarian Cancer Research Programme
- American Cancer Society Research Professor Award
- Frank McGraw Memorial Chair in Cancer Research
- MD Anderson Ovarian Cancer Research Fund
- Ann Rife Cox Chair in Gynecology
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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.
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