Risk of health-related quality of life events and pulmonary toxicities in recurrent ovarian cancer patients treated with poly adenosine diphosphate ribose polymerase (PARP) inhibitors maintenance

Abstract

Background: Pain and fatigue are the major determinants of health-related quality of life (HRQOL) in cancer patients undergoing chemotherapy. Ovarian cancer is the seventh most common cause of cancer in women worldwide. PARP inhibitors maintenance has shown to improve survival in recurrent ovarian cancer patients with notable toxicities. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of HRQOL events and pulmonary toxicities. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through March 2018. Phase III RCTs that mention HRQOL events and pulmonary toxicities as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Fixed effects model was applied. Results: Three phase III RCTs with a total of 1401 patients with recurrent ovarian cancer were eligible. The study arms used olaparib or niraparib or rucaparib while the control arms utilized placebo. The randomization ratio was 2:1 in all studies. The RR of allgrade side effects were as follows: fatigue, 1.54 (95% CI: 1.37 - 1.73, P<0.001); back pain, 0.93 (95% CI: 0.70 - 1.24, P=0.64); arthralgia, 1.05 (95% CI: 0.79 - 1.40, P=0.69); headache, 1.75 (95% CI: 1.34 - 2.29, P<0.001); decreased appetite, 1.76 (95% CI: 1.36 - 2.28, P<0.001); cough, 1.87 (95% CI: 1.33 - 2.63, P<0.001); dyspnea, 2.39 (95% CI: 1.64 - 3.48, P<0.001); and upper respiratory infections (URI), 1.71 (95% CI: 1.16 - 2.53, P=0.007). The RR of high-grade side effects were as follows: fatigue, 3.94 (95% CI: 1.90 - 8.17, P<0.001); back pain, 0.49 (95% CI: 0.10 - 2.48, P=0.39); arthralgia, 2.00 (95% CI: 0.22 - 17.82, P=0.53); headache, 1.00 (95% CI: 0.18 - 5.47, P=0.99); decreased appetite, 1.16 (95% CI: 0.17 - 7.82, P=0.87); and dyspnea, 1.28 (95% CI: 0.30 - 5.48, P=0.73). Conclusions: Our study showed that the risk of developing any-grade headache, decreased appetite, cough, dyspnea and URI as well as all grades of fatigue with PARP inhibitors was high. Prompt intervention with good supportive care is required.