Risk of hand-foot skin reaction with sorafenib: A systematic review and meta-analysis

Figures & data

Table I.  Characteristics of studies included in the meta-analysis.

Trial	Latest Publication	Trial Design	No. Enrolled	Age median (years)	Underlying Malignancy
Escudier et al. [16]	NEJM	Randomized phase III (Placebo vs Sorafenib)	903	58	RCC
Eisen et al. [49]	BJC	Randomized discontinuation phase II (Placebo vs Sorafenib)	37	53	Melanoma
Ratain et al. [3]	JCO	Randomized discontinuation phase II (Placebo vs Sorafenib)	202	58	RCC
Szczylik et al. [18]	2007 ASCO meeting	Randomized phase II (IFN vs Sorafenib)	189	62	RCC
Gatzemeier et al. [4]	2006 ASCO meeting	Single arm phase II	52	62	NSCLC
Wu et al. [17]	2006 Prostate Cancer symposium	Single arm phase II	22	64	Prostate
Ghassan et al. [5]	JCO	Single arm phase II	147	69	HCC
Figlin et al. [21]	2007 ASCO meeting	Expanded access program	2502	63	RCC
D'Adamo et al. [19]	2007 ASCO meeting	Single arm phase II	134	55	Non-GIST Sarcoma
Hobday et al. [22]	2007 ASCO meeting	Single arm phase II	93	59	Neuroendocrine tumors
Liovet et al. [20]	2007 ASCO meeting	Randomized phase III (Placebo vs Sorafenib)	602	66	HCC

Abbreviations: RCC, renal cell carcinoma; NSCLC, non-small cell lung cancer; HCC, hepatic cellular carcinoma; NEJM, New England Journal of Medicine; BJC, British Journal of Cancer. ASCO meeting, American Society of Clinical Oncology annual meeting.

Figure 1.  Annotated forest plot for meta-analysis of the incidence of hand-foot skin reaction (HFSR) in cancer patients who received sorafenib. The summary incidences of all-grade (A) and high-grade (B) HFSR are calculated using a random-effects model. The incidences and 95% confidence intervals for each study and the final combined result are displayed numerically on the left and graphically as a forest plot on the right. Under study name, the first author's name was used to represent each trial.

Figure 2.  Annotated forest plot for meta-analysis of the incidence of hand-foot skin reaction (HFSR) associated with sorafenib in patients with renal cell cancer. The summary incidences of all-grade (A) and high-grade (B) HFSR associated with sorafenib for patients with RCC are calculated using a random-effects model. The incidences and 95% confidence intervals for each study and the final combined result are displayed numerically on the left and graphically as a forest plot on the right. Under study name, the first author's name was used to represent each trial.

Figure 3.  Annotated forest plot for meta-analysis of the incidence of hand-foot skin reaction (HFSR) associated with sorafenib in patients with non-renal cell cancer. The summary incidence of all-grade (A) and high-grade (B) HFSR is calculated using a random-effects model. The incidences and 95% confidence intervals for each study and the final combined result are displayed numerically on the left and graphically as a forest plot on the right. Under study name, the first author's name was used to represent each trial.

Figure 4.  Relative risk (RR) of hand-foot skin reaction associated with sorafenib versus control in patients with metastatic renal cell carcinoma and hepatocellular carcinoma. The summary RR was calculated using a random-effects model. RR and 95% confidence intervals for each study and the final combined result are displayed numerically on the left and graphically as a forest plot on the right. Under study name, the first author's name was used to represent each trial.

Table II.  Association of hand-foot skin reaction with molecular targets.

Agent	Molecular Target	Incidence of HFSR
Bevacizumab	VEGF-A (interacting with VEGFR-1, 2) [49]	Minimal
Imatinib	Bcr-abl, C-Kit, PDGFRα, β tyrosine kinase [50]	rare
Sunitinib	VEGFR-1,-2; PDGFR, C-Kit, Flt-3, RET [51]	14 – 20% [52], [53]
Sorafenib	VEGFR-2,-3, Raf, PDGFR, C-Kit, Flt-3, RET	33.8%

Abbreviations: PDGFR, platelet derived growth factor receptor; VEGFR, vascular endothelial growth factor receptor; HFSR, Hand-Foot Skin Reaction. Targets shared by sunitinib and sorafenib but not imatinib and bevacizumab are bolded.

Figure 5.  Example of grades I (A), II (B), III (C) hand-foot skin reaction (HFSR) in patients receiving sorafenib.

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