Exploring and comparing adverse events between PARP inhibitors

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 P ARP inhibitors might certainly be warranted, a thorough understanding of all associated toxicities is imperative to ensure that patients can achieve maximal clinical benefit.

Poly(ADP-Ribose) Polymerase Inhibitors in Pancreatic Cancer: A New Treatment Paradigms and Future Implications

“…The differences in potency also correlate with their toxicity profiles [42,68]. The most common adverse events (AEs) are gastrointestinal, hematological and constitutional (fatigue).…”

Exploring the Synergy between PARP and CHK1 Inhibition in Matched BRCA2 Mutant and Corrected Cells

“…PARP inhibitors (PARPi) are a significant breakthrough in the treatment of cancer by exploiting cancer-specific defects in homologous recombination DNA repair (HRR), e.g., due to BRCA mutations. Toxicities associated with these drugs are generally mild [4]. Three PARPi are currently approved for the treatment of ovarian cancer, the success being largely due to the high frequency (>50%) of HRR defects in this cancer type [5][6][7].…”

Behandeling van prostaatkanker bij mannen met een somatische of BRCA-kiembaanmutatie

“…Andere studies in latere lijnen zijn de TRITON2 (NCT02952534), en de fase II-studie met talazoparib (TALAPRO-2). Metabolisering, interacties en toxiciteit van de PARP-remmers niraparib, rucaparib en olaparib zijn recentelijk beschreven in een fraai overzichtsartikel [24]. Het toxiciteitsprofiel van de PARP-remmers is vergelijkbaar voor het optreden van anemie ≥ 3 graad (19-25%), waarbij trombopenie ≥ 3 graad (34%) en neutropenie (20%) frequenter voorkomt bij niraparib dan bij de andere twee PARP-remmers.…”