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

Abstract

214 Background: Fatigue and pain notably contributed to the quality of life of cancer patients undergoing chemotherapy. Cabozantinib inhibits the activity of VEGFR, AXL, MET and other receptor tyrosine kinases which are essential in tumor development and progression. Yet the impact of this agent on fatigue and pain is a considerable safety concern. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine these risks. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception to March 2017 were queried. Phase 3 RCTs that mention fatigue, asthenia, back pain, pain in arms and legs, arthralgia, muscle spasm and bone and musculoskeletal pain 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: Three phase 3 RCTs with a total of 1999 patients were eligible for analysis. Studies compared cabozantinib (C) vs everolimus, C vs placebo, C vs prednisone, were included in the analysis. The relative risks (RR) of all-grade adverse effects were as follows: fatigue, 1.34 (95% CI: 1.19- 1.50, p < 0.0001); asthenia, 1.48 (95% CI: 1.06- 2.06, p = 0.02); back pain, 1.08 (95% CI: 0.84- 1.38, p = 0.52); pain in arms and legs, 1.44 (95% CI: 1.12- 1.84, p = 0.004); arthralgia, 0.98 (95% CI: 0.70- 1.36, p = 0.91); muscle spasm, 2.59 (95% CI: 1.63- 4.12, p < 0.0001); bone pain, 1.22 (95% CI: 0.35- 4.21, p = 0.74); and musculoskeletal pain, 0.64 (95% CI: 0.42- 0.96, p = 0.03). The RR of high-grade adverse effects were as follows: fatigue, 1.84 (95% CI: 1.36- 2.48, p < 0.0001); asthenia, 2.02 (95% CI: 1.37- 2.99, p < 0.0001); back pain, 1.17 (95% CI: 0.69- 1.98, p = 0.54); pain in arms and legs, 2.93 (95% CI: 1.12- 7.63, p = 0.02); arthralgia, 0.82 (95% CI: 0.39- 1.70, p = 0.59); bone pain, 1.20 (95% CI: 0.28- 5.10, p = 0.79); and musculoskeletal pain, 1.34 (95% CI: 0.38- 4.64, p = 0.64). Conclusions: Cabozantinib increased the risk of all-grade and high-grade fatigue, asthenia and pain in arms and legs as well as all-grade muscle spasm whereas the risk of musculoskeletal pain was lower in the study arm, favoring cabozantinib.