To identify the patient subgroups benefitting the most from the modern strategy including molecular-targeted therapy among patients with metastatic renal cell carcinoma (mRCC) in clinical practice.
Retrospective analysis of 144 patients with mRCC diagnosed between 1992 and 2011 at Kyoto University Hospital was conducted. Multivariate analysis using the Cox proportional hazards model was conducted to identify prognostic factors associated with overall survival (OS). Subgroup analysis was conducted to identify patients who benefitted the most from molecular-targeted therapy.
Independent factors associated with worse OS are: tumors of histological type other than clear-cell, decreased hemoglobin (Hb), elevated lactate dehydrogenase (LDH), elevated C-reactive protein (CRP), and metastases at ≥ 3 sites. Median OS of patients treated with molecular-targeted therapy alone or with prior immunotherapy and those treated with immunotherapy alone was 57, 45 and 28 months, respectively. Molecular-targeted therapy had more effect on OS than immunotherapy alone among female patients, patients with Memorial Sloan-Kettering Cancer Center (MSKCC) intermediate risk features, and patients with metastatic progression less than 1 year after initial diagnosis of RCC, compared with their counterparts.
The modern strategy including molecular-targeted therapy may improve OS in patients with mRCC and MSKCC intermediate risk features in clinical practice, relative to those with other risk features. However, the prognosis for patients with tumors of histological type other than clear-cell, decreased Hb, elevated LDH, elevated CRP, or metastases at ≥ 3 sites remains poor even in the modern molecular-targeted era. Novel treatment strategies are necessary to improve prognosis in these patients.
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Escudier B, Pluzanska A, Koralewski P et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111
Escudier B, Eisen T, Stadler WM et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134
Motzer RJ, Escudier B, Oudard S et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456
Rini BI, Escudier B, Tomczak P et al (2011) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378:1931–1939
Rini BI, Halabi S, Rosenberg JE et al (2008) Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26:5422–5428
Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281
Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068
Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124
Naito S, Yamamoto N, Takayama T et al (2010) Prognosis of Japanese metastatic renal cell carcinoma patients in the cytokine era: a cooperative group report of 1463 patients. Eur Urol 57:317–325
Shinohara N, Nonomura K, Abe T et al (2012) A new prognostic classification for overall survival in Asian patients with previously untreated metastatic renal cell carcinoma. Cancer Sci 103:1695–1700
Shinohara N, Abe T, Mochizuki T, et al. Is Memorial Sloan-Kettering Cancer Center risk classification appropriate for Japanese patients with metastatic renal cell carcinoma in the cytokine era? Urol Oncol. 2011 [E-pub ahead of print]
Kamba T, McDonald DM (2007) Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br J Cancer 96:1788–1795
Ravaud A (2011) Treatment-associated adverse event management in the advanced renal cell carcinoma patient treated with targeted therapies. Oncologist 16(Suppl 2):32–44
Cohen RB, Oudard S. Antiangiogenic therapy for advanced renal cell carcinoma: Management of treatment-related toxicities. Invest New Drugs. 2012; 30: 2066–79
La Vine DB, Coleman TA, Davis CH, Carbonell CE, Davis WB (2010) Frequent dose interruptions are required for patients receiving oral kinase inhibitor therapy for advanced renal cell carcinoma. Am J Clin Oncol 33:217–220
Yildiz I, Sen F, Basaran M et al (2011) Response rates and adverse effects of continuous once-daily sunitinib in patients with advanced renal cell carcinoma: a single-center study in Turkey. Jpn J Clin Oncol 41:1380–1387
van der Veldt AA, Boven E, Helgason HH et al (2008) Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer. Br J Cancer 99:259–265
Heng DY, Xie W, Regan MM et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27:5794–5799
Heng DY, Chi KN, Murray N et al (2009) A population-based study evaluating the impact of sunitinib on overall survival in the treatment of patients with metastatic renal cell cancer. Cancer 115:776–783
Warren M, Venner PM, North S et al (2009) A population-based study examining the effect of tyrosine kinase inhibitors on survival in metastatic renal cell carcinoma in Alberta and the role of nephrectomy prior to treatment. Can Urol Assoc J 3:281–289
Shek D, Tomlinson B, Brown M, Brunson A, Pan CX, Lara PN (2012) Epidemiologic trends in renal cell carcinoma in the cytokine and post-cytokine eras: a registry analysis of 28,252 patients. Clin Genitourin Cancer 10:93–98
Ljungberg B, Cowan NC, Hanbury DC et al (2010) EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 58:398–406
NCCN Clinical Practice Guidelines in Oncology Kidney Cancer Version 2.2012. [cited 2012 July 20]; Available from: http://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf
Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17:2530–2540
Motzer RJ, Hutson TE, Tomczak P et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590
Casamassima A, Picciariello M, Quaranta M et al (2005) C-reactive protein: a biomarker of survival in patients with metastatic renal cell carcinoma treated with subcutaneous interleukin-2 based immunotherapy. J Urol 173:52–55
Saito K, Tatokoro M, Fujii Y et al (2009) Impact of C-reactive protein kinetics on survival of patients with metastatic renal cell carcinoma. Eur Urol 55:1145–1153
Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296
Fujita T, Iwamura M, Ishii D, et al. C-reactive protein as a prognostic marker for advanced renal cell carcinoma treated with sunitinib. Int J Urol. 2012; 19: 908–13
Figlin R, Sternberg C, Wood CG. Novel agents and approaches for advanced renal cell carcinoma. J Urol. 2012; 188: 707–15
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The authors declare that they have no conflict of interest.
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Kamba, T., Yamasaki, T., Teramukai, S. et al. Improvement of prognosis in patients with metastatic renal cell carcinoma and Memorial Sloan-Kettering Cancer Center intermediate risk features by modern strategy including molecular-targeted therapy in clinical practice. Int J Clin Oncol 19, 505–515 (2014). https://doi.org/10.1007/s10147-013-0581-2
- Molecular-targeted therapy
- Renal cell carcinoma