Management of metastatic renal cell carcinoma in patients with poor prognosis

Figures & data

Table 1 Phase III trials of targeted therapy in advanced renal cell carcinoma

Agent	Trial	Size	Percent poor risk	Overall PFS (95% CI)	Overall response rate (95% CI)	Overall disease control rate
Sunitinib	Motzer 2007^Citation37	N = 750	6.4%	11 months (10–12)	31% (26–36)	79%
Sorafenib	Escudier 2007^Citation57	N = 903	0%	5.5 months	10% (7–13)	62% (57–66)
Temsirolimus	Hudes 2007^Citation35	N = 626	74%	5.5 months (3.9–7.0)	8.6% (4.8–12.4)	32.1% (25.7–38.4)
Everolimus	Motzer 2008^Citation36	N = 410	15%	4.0 months (3.7–5.5)	1%	64%
Bevacizumab/IFN	Escudier 2007^Citation38	N = 649	9%	10.2 months	31%	77%
Bevacizumab/IFN	Rini 2008^Citation39	N = 732	10%	8.5 months (7.5–9.7)	25.5% (20.9–30.6)

Table 2 Clinical prognostic criteria

Memorial Sloan Kettering Cancer Center Prognostic Criteria – version 1	Motzer 1999^Citation6	Corrected serum calcium Hemoglobin Karnofsky performance status Lactate dehydrogenase Prior nephrectomy
Memorial Sloan Kettering Cancer Center Prognostic Criteria – version 2	Motzer 2002^Citation4	Corrected serum calcium Hemoglobin Karnofsky performance status Lactate dehydrogenase Time from initial diagnosis to treatment with IFN-α
Cleveland Clinic	Mekhail 2005^Citation9	Corrected serum calcium Hemoglobin Lactate dehydrogenase Presence of liver, lung, or retroperitoneal nodal metastasis Prior radiotherapy Time from initial diagnosis to treatment with IFN-α
French Prognostic Criteria	Escudier 2002^Citation19	Alkaline phosphatase Corrected serum calcium Lactate dehydrogenase Number of metastatic sites Time from nephrectomy to metastatic disease

Figure 1 Survival curves from MSKCC and Cleveland Clinic criteria by prognostic category. Adapted with permission from Bukowski RM. Prognostic factors for survival in metastatic renal cell carcinoma: update 2008. Cancer. 2009;115(10 Suppl):2273–2281.59 Copyright © 2009 John Wiley & Sons, Inc.

Table 3 Biomarkers of prognosis in renal cell carcinoma

Histology

Clear cell

Chromophobe

Papillary

Sarcomatoid

Molecular biomarkers

CAIX tumor expression

p53 tumor expression

PTEN tumor expression

Vimentin tumor expression

pAKT tumor expression

IMP3 tumor expression

B7H1/B7H4 tumor expression

Genetic biomarkers

VHL mutation, deletion, and/or hypermethylation

Table 4 Results of an analysis of OS by individual baseline factors

Factor	OS		P
	HR	95% CI
Treatment (sunitinib vs IFN-α)	0.764	0.623–0.936	0.0096
ECOG PS (1 vs 1)	0.515	0.417–0.636	<0.0001
Hemoglobin (≥ vs < LLN)	0.504	0.401–0.634	<0.0001
Time from diagnosis to treatment (≥ vs < 1 year)	0.574	0.461–0.715	<0.0001
Corrected calcium (≤ vs > 10 mg/dL)	0.466	0.327–0.664	<0.0001
Alkaline phosphatase (≤ vs > ULN)	0.676	0.542–0.844	0.0005
Lactate dehydrogenase (≤ vs > 1.5 × ULN)	0.500	0.337–0.742	0.0006
No of metastastic sites (1 vs ≥ 2)	0.664	0.503–0.876	0.0037

Abbreviations: CI, confidence interval; HR, hazard ratio; ULN, upper limits of normal; ECOG, Eastern Cooperative Oncology Group.

Reprinted from with permission. Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with etastatic renal cell carcinoma. J Clin Oncol. 2009;27(22):3584–3590. Copyright © 2009 American Society of Clinical Oncology. All Rights Reserved.

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