Abstract
There are many active drugs to treat metastatic renal cell carcinoma (mRCC) patients who progress through their first-line vascular endothelial growth factor (VEGF) inhibitor. Many clinicians choose a second-line VEGF inhibitor based on the type of response to first-line VEGF inhibitor, without data supporting this practice. This study was conducted to determine the association of response to second-line VEGF inhibitor with response to first-line VEGF inhibitor. All mRCC patients in participating centers of the International mRCC Database Consortium who were treated from January 2004 through June 2011 with a second-line VEGF inhibitor after failure of a different first-line VEGF inhibitor were retrospectively identified. The primary outcome is objective response rate (ORR) and the secondary outcome is progression-free survival (PFS) in each line of therapy. Of 1,602 total database patients, 464 patients received a first- and second-line VEGF inhibitor. The ORR to first-line therapy was 22 %, and the ORR to second-line therapy was 11 %. The ORR to second-line therapy was not different among patients achieving partial response versus stable disease versus progressive disease to first-line therapy (14 % vs. 10 % vs. 11 %, respectively; chi-squared trend test p = 0.17). The median PFS on first-line VEGF-targeted therapy was 7.5 months (95 % CI, 6.6–8.1), and the median PFS on second-line VEGF inhibitor was 3.9 months (95 % CI, 3.6–4.5). There was no correlation between first-line and second-line PFS (Pearson correlation coefficient 0.025; p = 0.59). The clinical response to a second-line VEGF inhibitor is not dependent on response to the first-line VEGF-inhibitor. Further studies are needed to define clinical parameters that predict response to second-line therapy to optimize the sequence of VEGF-targeted therapy in metastatic RCC patients.
Similar content being viewed by others
References
Escudier B, Bellmunt J, Negrier S et al (2010) Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 28(13):2144–2150
Rini BI, Halabi S, Rosenberg JE et al (2010) Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol 28(13):2137–2143
Al-Marrawi MY, Rini BI (2011) Pazopanib for the treatment of renal cancer. Expert Opin Pharmacother 12(7):1171–1189
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(6):1061–1068
Escudier B, Szczylik C, Hutson TE et al (2009) Randomized phase II trial of first-line treatment with sorafenib versus interferon alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol 27(8):1280–1289, Erratum in J Clin Oncol. 2009 May 1; 27(13):2305
Escudier B, Eisen T, Stadler WM et al (2009) Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 27(20):3312–3318
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
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(22):3584–3590
Rini BI, Wilding G, Hudes G et al (2009) Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol 27(27):4462–4468
Rini BI, Wilding GT, Hudes G et al (2007) Axitinib (AG-013736; AG) in patients (pts) with metastatic renal cell cancer (RCC) refractory to sorafenib [abstract]. J Clin Oncol 25(Suppl 1):Abstract 5032
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(9807):1931–1939, Epub 2011 Nov 4
Motzer RJ, Bacik J, Schwartz LH et al (2004) Prognostic factors for survival in previously treated patients with metastatic renal cell cancer. J Clin Oncol 22(3):454–463
Motzer RJ, Escudier B, Oudard S et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomized, placebo-controlled phase III trial. Lancet 372(9637):449–456, Epub 2008 Jul 22
Porta C, Paglino C, Imarisio I (2010) Sequencing tyrosine kinase inhibitors or immediately switching to mTOR inhibitors in advanced kidney cancer: a critical review. Eur J Clin Med Oncol 2:1–6, 2010
Busch J, Seidel C, Kempkensteffen C et al (2011) Sequence therapy in patients with metastatic renal cell carcinoma: comparison of common targeted treatment options following failure of receptor tyrosine kinase inhibitors. Eur Urol 60(6):1163–1170
Heng DYC, 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(34):5794–5799
Smith AD, Shah SN, Rini BI, Lieber ML, Remer EM (2010) Morphology, Attenuation, Size, and Structure (MASS) criteria: assessing response and predicting clinical outcome in metastatic renal cell carcinoma on antiangiogenic targeted therapy. AJR Am J Roentgenol 194(6):1470–1478
Krajewski KM, Guo M, Van den Abbeele AD et al (2011) Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma. Eur Urol 59(5):856–862
Motzer RJ, Escudier B, Oudard S et al (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116(18):4256–4265
Conflict of interest
This study received no direct or indirect industry or pharmaceutical company support. The following authors have indicated a financial interest that is relevant to this study or to the subject matter under consideration in this article (consultant or advisory role (C), Honoraria (H), research funding (R))—Brian I. Rini: Bayer/Onyx, Roche (C) and GSK, Pfizer (C, R). Lori Wood: Pfizer and Novartis (C, R). Georg A. Bjarnason: Pfizer Canada (C, H, and R), Novartis (C, H), GSK (C, H). Lauren C. Harshman: Novartis, Pfizer (C on advisory board); BMS, Genentech, Novartis (R). Ulka Vaishampayan: Pfizer, Novartis and GSK (H & R). Jennifer J. Knox: AVEO (C), Novartis (R), Pfizer (C, R), Bayer (R). Daniel Heng: Pfizer, Novartis, Bayer (C, H). All remaining authors have declared no conflicts of interest.
Author information
Authors and Affiliations
Consortia
Corresponding author
Additional information
This study was presented at ASCO on June 7th, 2011 in Chicago, IL, USA.
Rights and permissions
About this article
Cite this article
Al-Marrawi, M.Y., Rini, B.I., Harshman, L.C. et al. The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients. Targ Oncol 8, 203–209 (2013). https://doi.org/10.1007/s11523-012-0252-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11523-012-0252-7