Meta-Analysis of PARP-Inhibitor–Associated Gastrointestinal and Hepatic Toxicities
For cancer cells of ovarian tumors that are deficient in homologous recombination, the inhibition of poly (ADP-ribose) polymerase (PARP) enzymes can result in synthetic lethality by terminating an alternative DNA repair pathway. Although PARP inhibitors have been shown to improve patient survival for a variety of cancer types, their associated safety concerns can negatively affect patient quality of life. In this study, Thein and colleagues undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) published before March 2018 to determine the risk for gastrointestinal (GI) and hepatic toxicities.
In the 3 included phase 3 RCTs with mention of GI toxicities and elevation of liver function tests (LFTs), 1401 patients were eligible. The included study arms used the PARP inhibitors―olaparib, niraparib, or rucaparib―and the control arms utilized placebo, and each of the 3 studies used a 2:1 active:control randomization ratio. The meta-analysis showed that PARP inhibitors increased the risk for all grades of GI and hepatic toxicities, with relative risks (RRs) of 1.29 for diarrhea (95% confidence interval [CI], 1.05-1.58; P = .015), 1.73 for dyspepsia (95% CI, 1.20-2.49; P = .003), 2.11 for nausea (95% CI, 1.86-2.40; P <.001), 2.20 for vomiting (95% CI, 1.76-2.75; P <.001), 4.38 for dysgeusia (95% CI, 3.00-6.41; P <.001), and 4.74 for elevated LFT (95% CI, 2.82-7.95; P <.001). High-grade (grades 3 and 4) side effects were also increased, with RRs of 1.225 for diarrhea (95% CI, 0.992-1.512; P = .060), 4.35 for nausea (95% CI, 1.45-13.06; P = .009), 3.39 for vomiting (95% CI, 1.19-9.63; P = .02), and 10.19 for elevated LFT (95% CI, 2.47-42.06; P = .001).
Given the significant impact that these toxicities may have on patients’ quality of life, and that they may negatively affect compliance rates, the authors suggest that timely intervention with proper supportive care should be considered for patients receiving treatment with PARP inhibitors.
Thein KZ, et al. ESMO 2018. Abstract 969P.