Risk of mucocutaneous toxicities in patients with solid tumors treated with sorafenib: an updated systematic review and meta-analysis

Abstract

We performed a systematic review and meta-analysis of mucocutaneous toxicities associated with sorafenib, an oral multi tyrosine kinase inhibitor. Eligible studies included randomized Phase II and III trials of patients with solid tumors on sorafenib daily describing events of hand foot skin reaction, skin rash, alopecia, stomatitis or pruritis. Patients treated with sorafenib had a significantly increased risk of all-grade mucocutaneous toxicities. The RR of all-grade hand foot skin reaction, skin rash, alopecia, stomatitis and pruritis were 4.33 (95% CI: 3.06–6.14), 2.67 (95% CI: 1.86–3.83), 3.93 (95% CI: 2.07–7.45), 2.9 (95% CI: 2.26–3.73), 2.29 (95% CI: 1.87–3.03); respectively. Exploratory subgroup analysis showed no effect of tumor types or treatment regimen (monotherapy versus combination) on the RR of mucocutaneous toxicities. Our meta-analysis has demonstrated that sorafenib is associated with a higher risk of developing all grade mucocutaneous toxicities compared with control.

Keywords::

• alopecia
• hand-foot skin reaction
• meta-analysis
• mucocutaneous toxicities
• skin rash
• sorafenib
• stomatitis or pruritus

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Sorafenib is an orally active multityrosine kinase inhibitor that targets multiple angiogenic and tumorigenic pathways.

• Currently, the US FDA has approved sorafenib for patients with advanced hepatocellular carcinoma, metastatic renal cell carcinoma as well as radioiodine refractory differentiated thyroid carcinoma.

• VEGF receptor tyrosine kinase inhibitors, including sorafenib, have been linked to a unique spectrum of adverse events, most notably including mucocutaneous adverse events.

• In this review, we performed a systematic review and meta-analysis of mucocutaneous toxicities associated with sorafenib.

• Eligible studies included randomized Phase II and III trials of patients with solid tumors on sorafenib, describing events of hand-foot skin reaction, skin rash, alopecia, stomatitis or pruritus.

• After proper selection of the studies, a total of 17 randomized clinical trials were considered eligible for the meta-analysis.

• Patients treated with sorafenib had a significantly increased risk of all-grade mucocutaneous toxicities including hand-foot skin reaction, skin rash, alopecia, stomatitis or pruritus.

• Subgroup analyses showed no difference in the relative risk for combination regimens compared with monotherapy.

• Clinicians should be aware of these risks and perform regular mucocutaneous monitoring.