Program Description
Ongoing research continues to investigate novel therapies to improve outcomes for patients with advanced renal cell carcinoma (RCC). Various combination strategies are being evaluated that target RCC either through different pathways or through different points along the same pathway. Novel targeted agents are also being assessed, with several demonstrating potentially promising activity in advanced RCC. In this CME-certified webinar, Dr. Gary R. Hudes and Dr. Robert A. Figlin discuss the potential benefits and challenges of these new approaches. They also discuss other timely issues in advanced RCC, including the role of cytoreductive nephrectomy with targeted therapy and new approaches to adjuvant therapy.

Target Audience
This activity has been designed for community oncologists, urologists, nephrologists and allied healthcare professionals who provide care and support to patients with advanced RCC.

Learning Objectives
After completing this activity, participants should be able to

	•	Discuss the rationale for various combination therapy approaches in the treatment of advanced RCC
	•	Describe the use of novel targeted agents in the treatment of advanced RCC
	•	Discuss planned and ongoing phase III trials in advanced and locally advanced RCC

Faculty
Robert A. Figlin, MD (Activity Director)
Arthur and Rosalie Kaplan Chair in Oncology
Professor and Chair, Medical Oncology and Therapeutics Research
City of Hope National Medical Center and Beckman Research Institute
Associate Director for Clinical Research
City of Hope National Medical Center
Duarte, California

Gary R. Hudes, MD
Director, Genitourinary Malignancies Program
Fox Chase Cancer Center
Philadelphia, Pennsylvania

Accreditation
This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the City of Hope and Alliance Medical Communications. The City of Hope is accredited by the ACCME to provide continuing medical education for physicians.

Designation of Credit
The City of Hope designates this educational activity for 1 AMA Physicians’ Recognition Award^™ credit. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Disclosure
City of Hope takes responsibility for the content, quality and scientific integrity of this continuing medical education (CME) activity. Prior to their participation in this City of Hope CME activity, all faculty/presenters have disclosed any real or apparent vested commercial interest(s) in both those companies whose products may be discussed during the course of the activity and in those companies acting as commercial supporters of the activity. City of Hope further requires that prior to the activity, faculty/presenters have disclosed their intention to discuss any off-label and/or investigational (not yet approved for any purpose) use of pharmaceuticals or medical devices. Written disclosure of faculty/presenters’ specific commercial relationships and/or intent to discuss off-label and/or investigational is provided below.

Robert A. Figlin, MD (Activity Director)

Commercial Interest	Relationship
Aveo Pharmaceuticals	Consultant
Amgen, Argos Therapeutics, Antisoma plc, Novartis AG; Pfizer Inc	Grant/Research Support

Gary R. Hudes, MD

Commercial Interest	Relationship
Genentech; Novartis AG; Pfizer Inc; Wyeth	Consultant
Pfizer Inc	Speakers’ Bureau

Independent Clinical Peer Reviewer
Robert J. Morgan Jr., MD
Director, Continuing Medical Education
Associate Director for Education
Department of Oncology and Therapeutics Research
City of Hope National Medical Center
Duarte, California

Planning Committee
Crystal Saavedra, City of Hope National Medical Center and Deborah Dean, Mindy Tanzola, PhD, and Michelle Yechout, Alliance Medical Communications: No relevant financial relationships with any commercial interests.

Off-label Use
The following is a list of specific mention of off-label and/or investigational use of products within all presentations.

Product	Investigational and/or Off-Label Use
AV951	Renal cell carcinoma for patients with no prior VEGF
Axitinib	Renal cell carcinoma for sorafenib-refractory patients
Bevacizumab	Renal cell carcinoma
CP-675,206 (tremelimumab)	Metastatic renal cell carcinoma
Dasitinib	Unresectable/metastatic tumors
Erlotinib	Advanced/metastatic renal cell carcinoma
Gefitinib	Metastatic renal cell carcinoma
IFN-α	Renal cell carcinoma
Pazopanib	Advanced renal cell carcinoma
Vitespen	Renal cell carcinoma
WX-G250	Renal cell carcinoma

References

1.	Atzpodien J, Schmitt E, Gertenbach U, et al. Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). Br J Cancer. 2005;92:843-846.
2.	Bhargava P et al. Updated activity and safety results of a phase II randomized discontinuation trial (RDT) of AV-951, a potent and selective VEGFR1, 2, and 3 kinase inhibitor, in patients with renal cell carcinoma (RCC). J Clin Oncol. 2009;27(15s):A5032.
3.	Biswas S, Kelly J, Eisen T. Cytoreductive nephrectomy in metastatic clear-cell renal cell carcinoma: perspectives in the tyrosine kinase inhibitor era. Oncologist. 2009;14(1):52-59.
4.	Bracarda S, Porta C, Boni C, et al. Randomized prospective phase II trial of two schedules of sorafenib daily and interferon-a2a (IFN) in metastatic renal cell carcinoma (RAPSODY): GOIRC Study 0681. J Clin Oncol. 2007;25(18S):A5100.
5.	Bukowski RM, Kabbinavar FF, Figlin RA et al. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007;25(29):4536-4541.
6.	Clark JI, Atkins MB, Urba WJ, et al. Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: a cytokine working group randomized trial. J Clin Oncol. 2003;21:3133-3140.
7.	Escudier BJ et al. Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon (IFN)-??2a in metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2009; 27(15S): A5020.
8.	Escudier B, Pluzanska A, Koralewski P et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370(9605):2103-2111.
9.	Feldman DR, Kondagunta GV, Ronnen EA, et al. Phase I trial of bevacizumab plus sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2008;26(May 20 suppl): abstract 5100.
10.	Figlin RA, Hutson TE, Tomczak P. et al. Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2008;26(May 20 suppl): abstract 5024.
11.	Garcia JA, Cooney MM, Mekhail T, et al. Sunitinib and bevacizumab in advanced solid tumors: preliminary results of a phase I trial. Program and abstracts of the 2008 ASCO Genitourinary Cancers Symposium. Abstract 352.
12.	Gollob JA, Rathmell WK, Richmond TM, et al. Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J Clin Oncol. 2007;25:3288-3295.
13.	Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271-2281.
14.	Hutson TE, Davis ID, Machiels JH et al. Biomarker analysis and final efficacy and safety results of a phase II renal cell carcinoma trial with pazopanib (GW786034), a multi-kinase angiogenesis inhibitor. J Clin Oncol. 2008;26(May 20 suppl):A5046.
15.	Jonasch E, Corn P, Ashe RG et al. Randomized phase II study of sorafenib with or without low-dose IFN in patients with metastatic renal cell carcinoma. J Clin Oncol. 2007;25(18S):A5104.
16.	Kay A, Motzer R, Figlin R et al. Updated data from a phase III randomized trial of everolimus (RAD001) versus PBO in metastatic renal cell carcinoma (mRCC). 2009 ASCO Genitourinary Cancers Symposium, abstract 278.
17.	Kondagunta GV, Hudes GR, Figlin R et al. Sunitinib malate (SU) plus interferon (IFN) in first line metastatic renal cell cancer (mRCC): Results of a dose-finding study. J Clin Oncol. 2007; 25(18S):A5101.
18.	Merchan JR, G. Liu, T. Fitch, J. Picus et al. Phase I/II trial of CCI-779 and bevacizumab in stage IV renal cell carcinoma: Phase I safety and activity results. J Clin Oncol. 2007;25(18S):A5034
19.	Messing EM, Manola J, Wilding G, et al. Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. J Clin Oncol. 2003;21:1214-1222.
20.	Pizzocaro G, Piva L, Colavita M, et al. Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. J Clin Oncol. 2001;19:425-431.
21.	Rini BI et al. Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma: Results of overall survival for CALGB 90206. J Clin Oncol. 2009;27(18S):A-LBA5019.
22.	ini BI, Halabi S, Rosenberg JE, Stadler WM, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008;26(33):5422-5428.
23.	Rini BI, Wilding GT, Hudes G et al. Axitinib (AG-013736; AG) in patients (pts) with metastatic renal cell cancer (RCC) refractory to sorafenib. J Clin Oncol. 2007;25(18S):A5032.
24.	Rosenberg JE, Weinberg VK, Claros C et al. Phase I study of sorafenib and RAD001 for metastatic clear cell renal cell carcinoma. J Clin Oncol. 2008;26(May 20 suppl):A5109.
25.	Ryan CW, Goldman BH, Lara PN Jr, et al. Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase II study of the Southwest Oncology Group. J Clin Oncol. 2007;25:3296-3301.
26.	Search for Clinical Trials. A US National Institutes of Health website. Available at: http://www.clinicaltrials.gov. Accessed May 14, 2009.
27.	Sosman JA, Flaherty KT, Atkins MB. Updated results of phase I trial of sorafenib (S) and bevacizumab (B) in patients with metastatic renal cell cancer (mRCC). J Clin Oncol. 2008;26(May 20 suppl):A5011.
28.	Stadler WM. Targeted agents for the treatment of advanced renal cell carcinoma. Cancer. 2005;104:2323-2333.
29.	Sternberg CN et al. A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). J Clin Oncol. 2009; 27(15S): A5021.
30.	Szczylik C, Demkow T, Staehler M et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon in patients with advanced renal cell carcinoma: Final results. J Clin Oncol. 2007;25(18S): abstract 5025.
31.	Szczylik C, Porta C, Bracarda S et al. Sunitinib in patients with or without prior nephrectomy (Nx) in an expanded access trial of metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2008;26(May 20 suppl):A5124.
32.	van der Veldt AA, Meijerink MR, van den Eertwegh AJ et al. Sunitinib for treatment of advanced renal cell cancer: primary tumor response. Clin Cancer Res. 2008;14(8):2431-2436.
33.	Whorf RC, Hainsworth JD, Spigel DR et al. Phase II study of bevacizumab and everolimus (RAD001) in the treatment of advanced renal cell carcinoma (RCC). J Clin Oncol. 2008;26(May 20 suppl):A5010.
34.	Wood C, Srivastava P, Bukowski R et al. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet. 2008;372(9633):145-154.