A systematic review and meta-analysis of randomized controlled trials to evaluate the risk of fatigue and pain among patients treated with ibrutinib.

Abstract

213 Background: Bruton’s tyrosine kinase (BTK), a kinase downstream of the B-cell receptor, involves in the B cell survival and proliferation and has become an attractive therapeutic target. Ibrutinib is an oral potent, covalent inhibitor of BTK and hence employed in many hematologic malignancies. We performed a systematic review and pooled analysis of randomized controlled trials (RCTs) to determine the risk of fatigue and pain among patients treated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts through December 31, 2016. RCTs that mention fatigue, arthralgia, muscle spasm, back pain, pain in extremity and myalgia as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: Four phase 3 RCTs with a total of 1505 patients were eligible for the analysis. Studies compared Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B)+ rituximab (R) vs placebo + B+ R and I vs temsirolimus were included in the analysis. The relative risks (RR) of all-grade side effects were as follows: fatigue, 0.87 (95% CI: 0.74- 1.03, p = 0.11); arthralgia, 1.97 (95% CI: 1.11- 3.50, p = 0.02); muscle spasm, 1.92 (95% CI: 1.22- 3.02, p = 0.005); back pain, 1.56 (95% CI: 1.02- 2.37, p = 0.03); pain in extremity, 2.47 (95% CI: 1.14- 5.36, p = 0.02); and myalgia, 2.68 (95% CI: 1.18- 6.05, p = 0.01). The RR of high-grade side effects were as follows: fatigue, 0.70 (95% CI: 0.37- 1.33, p = 0.28); arthralgia, 3.62 (95% CI: 0.74- 17.66, p = 0.11); back pain, 2.80 (95% CI: 0.42- 18.35, p = 0.28); pain in extremity, 2.96 (95% CI: 0.31- 28.4, p = 0.34); and myalgia, 2.96 (95% CI: 0.31- 28.44, p = 0.34). Conclusions: Our meta-analysis demonstrated that the risk of all-grade arthralgia, muscle spasm, back pain, pain in extremity and myalgia with ibrutinib was high. Pain is a major determinant of quality of life in cancer patients undergoing chemotherapy and recognizing these may help clinicians in delivering proper supportive care.