Risk of treatment-related mortality with sorafenib in cancer patients: a meta-analysis of 20 randomly controlled trials
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Background Sorafenib is a relatively new multi-kinase inhibitor used to treat a wide range of cancers. As fatal adverse events from sorafenib therapy are rare, their investigation requires a meta-analysis. Aim of the review To provide a meta-analysis of sorafenib-associated fatal adverse events with the most expansive and current data. Method We searched Medline, EMBASE, Web of Science and Cochrane Library databases. We also searched abstracts from a number of conferences. Twenty trials of sorafenib were found in 9434 cancer patients, tested against placebos and against other drugs. We calculated relative risks and incidences for sorafenib-associated mortality. Results Overall incidence of sorafenib-associated mortality was 3.3 %. Patients with renal cell carcinoma (RCC) and thyroid cancer had treatment-related mortality ≥5 %. Patients treated with sorafenib had a significantly greater risk of mortality than those in placebo/control groups, with an RR of 1.75. Subgroup analyses also showed significant differences in sorafenib versus placebo (RR 1.87, 95 % CI 1.23–2.86; I 2 = 0.0 %, P = 0.865); and sorafenib + platinum-based chemotherapy (RR 2.03, 95 % CI 1.15–3.59; I 2 = 0.0 %, P = 0.654). However, sorafenib had lower risk than other multi-targeted antiangiogenic tyrosine kinase inhibitors. Patients with RCC and non-small-cell lung carcinoma were significantly more vulnerable. Conclusion Sorafenib presents a significant risk of fatal adverse events (FAEs) in patients with cancer, especially for RCC or non-small-cell lung carcinoma, and in patients treated with sorafenib + platinum-based chemotherapy. However, compared with other multi-targeted antiangiogenic tyrosine kinase inhibitors, sorafenib has a lower risk of FAEs.
KeywordsAdverse events Meta-analysis Mortality Relative risk Sorafenib Tyrosine kinase inhibitors
We thank Edanz for its linguistic assistance during the preparation of this manuscript.
No special funding was received for this review.
Conflicts of interest
The authors have no conflict of interest.
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