1 / 65

Part III – Renal Cell Carcinoma Thursday, September 13, 2012 7:30 PM – 8:30 PM ET

braden
Download Presentation

Part III – Renal Cell Carcinoma Thursday, September 13, 2012 7:30 PM – 8:30 PM ET

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Please note, these are the actual video-recorded proceedings from the live CME event and may include the use of trade names and other raw, unedited content. Select slides from the original presentation are omitted where Research To Practice was unable to obtain permission from the publication source and/or author. Links to view the actual reference materials have been provided for your use in place of any omitted slides.

  2. RTP TV: A Live CME Webcast Series Focused on Emerging Data Sets and Novel Therapeutic Strategies in the Management of Common Cancers Part III – Renal Cell Carcinoma Thursday, September 13, 20127:30 PM – 8:30 PM ET

  3. Neil Love, MDResearch To PracticeMiami, Florida Thomas E Hutson, DO, PharmD Director, GU Oncology Program Co-Director, GU Center of Excellence, Texas Oncology, PA Charles A Sammons Cancer Center and Baylor University Medical Center Professor of Medicine, Texas A&M Health Science Center College of Medicine Co-Chair of GU Research, US Oncology Dallas, Texas Robert J Motzer, MD Medical Oncologist Memorial Sloan-Kettering Cancer Center New York, New York

  4. Agenda —Renal Cell Carcinoma New Developments in mRCC Anti-PD-1 Tivozanib Axitinib Cabozantinib Pazopanib Algorithm for Selecting Systemic Therapy Management of Toxicities with Novel Agents mTOR inhibitors TKIs

  5. New Developments in mRCC

  6. At this time, there is no known tissue or serum predictor of response to anti-PD-1.

  7. Blockade of T-Cell Signaling in Tumor Immunotherapy Ribas A et al. N Engl J Med 2012;366(26):2517-9.

  8. Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with previously treated metastatic renal cell carcinoma (mRCC) McDermott DF et al. Proc ASCO 2012;Abstract 4505.

  9. Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer Topalian SL et al. N Engl J Med 2012;366(26):2443-54. Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer Brahmer JR et al. N Engl J Med 2012;366(26):2455-65.

  10. Phase I Studies of Anti-PD-1/PD-L1 Agents: Advanced RCC Patient Subgroup a Topalian SL et al. N Engl J Med 2012;366(26):2443-54. b Brahmer JR et al. N Engl J Med 2012; 366(26):2455-65.

  11. Anti-PD-1 Treatment-Related Adverse Events: Advanced RCC Patient Subgroup (n = 34) *All doses of anti-PD-1 † Most common Grade 3-4 AEs were respiratory system disorders (2 pts) and hypophosphatemia (2 pts). McDermott DF et al. Proc ASCO 2012;Abstract 4505.

  12. Relative Potencies of TKIs Eskens FALM et al. Proc AACR 2008;Abstract LB-201; Nakamura K et al. Cancer Res 2006;66:9134-42; Chow LQ et al. J Clin Oncol 2007;25:884-96; Lee SH et al. Clin Cancer Res 2005;11:3633-41.

  13. Tivozanib is associated with fewer side effects and is more tolerable than sorafenib.

  14. Tivozanib: Summary of Key Attributes • Potent pan-VEGFR inhibitor • Highly selective TKI for the VEGF receptors • Favorable pharmacokinetic profile that enables once-daily dosing • Oral administration Chow LQ et al. J Clin Oncol 2007;25:884-96. Eskens FALM et al. Proc AACR 2008;LB-201.

  15. Tivozanib versus Sorafenib as Initial Targeted Therapy for Patients with Advanced Renal Cell Carcinoma: Results from a Phase III Randomized, Open-Label, Multicenter Trial Motzer RJ et al. Proc ASCO 2012;Abstract 4501.

  16. Primary endpoint: Progression-free survival superiority of tivozanib TIVO-1: A Phase III Trial of First-Line Tivozanib versus Sorafenib in Advanced RCC R Tivozanib (n = 260) Advanced RCC Clear cell histology Prior nephrectomy No prior VEGF or mTOR therapy Sorafenib (n = 257) Progression Crossover to tivozanib via separate protocol Motzer RJ et al. Proc ASCO 2012;Abstract 4501.

  17. TIVO-1: Progression-Free Survival Probability of PFS Time (months) With permission from Motzer RJ et al. Proc ASCO 2012;Abstract 4501.

  18. TIVO-1: Treatment-Emergent Adverse Events Fewer dose interruptions and reductions and treatment discontinuations occurred on the tivozanib arm. Motzer RJ et al. Proc ASCO 2012;Abstract 4501.

  19. Sorafenib: Reported Progression-FreeSurvival Values Over Time EU-ARCCS ECOG-0 (Expanded Access) 9.2 AMG 386 (PH2) and Japan CI. Exp. 9.0 Japan (PH2) NA-ARCCS(ExpandedAccess) RDD (PH2) Italian Clinical Experience 8.4 8.3 7.4 6.6 EU-ARCCS Overall (Expanded Access) 6.7 5.7 5.5 6.5 AXIS/PriorCytokine(PH3) Reported Median PFS (Months) Sorafenib vs IFN(PH2) Target (PH3) Publication Year Yellow = includes treatment naïve patientsGray = prior treatment with cytokine therapy and/or selective therapy targeting the angiogenesis pathway With permission fromEisen T. ASCO 2012 Discussant

  20. Sorafenib Studies Safety Eisen T. ASCO 2012 Discussant

  21. Primary endpoint: Patient preference for tivozanib or sunitinib after having received both in sequence Secondary endpoints: Safety, frequency of dose modifications and quality of life TAURUS: A Phase II Crossover-Controlled Study of First-Line Tivozanib versus Sunitinib in Advanced RCC R Target Accrual: 160 (Open) Sunitinib Tivozanib Untreated, advanced RCC 1:1 Sunitinib Tivozanib www.clinicaltrials.gov. Accessed September 2012.

  22. Primary outcome measures: Correlation of predefined biomarkers for tivozanib activity present in blood and tumor tissue with clinical activity and/or treatment-related toxicity Progression-free survival rate at 6 months BATON: A Phase II Biomarker Assessment of Tivozanib in Oncology Trial in Patients with Advanced RCC Trial Identifier: NCT01297244 Target Accrual: 105 (Closed) Unresectable locally recurrent or metastatic RCC Prior nephrectomy ≤1 prior systemic therapy (no prior VEGF- or mTOR-targeted therapy) Tivozanib Hutson TE et al. Proc ASCO 2012;Abstract TPS4686.

  23. There is a significant association between the development of hypertension and the antitumor benefit with axitinib.

  24. Comparative Effectiveness of Axitinib versus Sorafenib in Advanced Renal Cell Carcinoma (AXIS): A Randomised Phase 3 Trial Rini B et al. Lancet 2011;378(9807):1931-9.

  25. AXIS: Progression-Free Survival in Patients with RCC Receiving Second-Line Axitinib or Sorafenib Rini B et al. Lancet 2011;378(9807):1931-9.

  26. Axitinib for First-Line Metastatic RCC: Overall Efficacy and Pharmacokinetic Analyses from a Randomized Phase II Study Rini BI et al. Proc ASCO 2012;Abstract 4503.

  27. Clinical Outcome According to Diastolic Blood Pressure on Cycle 1 Day 15 a Geometric mean dBP = diastolic blood pressure (per ambulatory blood pressure monitoring); ΔdBP = change in dBP from baseline Rini BI et al. Proc ASCO 2012;Abstract 4503.

  28. Cabozantinib has resulted in bone scan and symptom improvements in prostate cancer but no other solid tumor.

  29. Efficacy of Cabozantinib (XL184) in Patients with Metastatic, Refractory Renal Cell Carcinoma Choueiri TK et al. Proc ASCO 2012;Abstract 4504.

  30. Partial Bone Scan Resolution and Pain Relief in a Symptomatic Patient with Bone Metastases Prior therapies include sorafenib, everolimus, and sunitinib Baseline 7-week follow-up • Patient substantially reduced narcotic use by 7 weeks; continued on reduced narcotics until week 25 • Another patient with bone metastases and pain at baseline reported complete resolution of pain by 4 weeks • Pain free 90+ weeks on study With permission from Choueiri TK et al. Proc ASCO 2012;Abstract 4504.

  31. Cabozantinib Efficacy Summary DCR = disease control rate defined as partial response + stable disease at 16 weeks Choueiri TK et al. Proc ASCO 2012;Abstract 4504.

  32. Pazopanib has about the same efficacy as sunitinib as first-line treatment but is strongly preferred by patients.

  33. Patient Preference between Pazopanib (Paz) and Sunitinib (Sun): Results of a Randomized Double-Blind, Placebo-Controlled, Cross-Over Study in Patients with Metastatic Renal Cell Carcinoma (mRCC) — PISCES Study, NCT 01064310 Escudier BJ et al. Proc ASCO 2012;Abstract CRA4502.

  34. R Study Design Period 1 Period 2 Pazopanib800 mg OD Sunitinib 50 mg 4/2a Patient preference for further treatment 1:1 N = 169 Sunitinib 50 mg 4/2a Pazopanib800 mg OD 10 weeks 2-weekwashout 10 weeks End of study Double-blind phase 0 10 12 22 Stratification factors: • ECOG PS (0 vs 1) • Metastatic sites (1 vs ≥2) Time (weeks) a 4 weeks on treatment  2 weeks matching placebo  4 weeks on treatment. ECOG PS, Eastern Cooperative Oncology Group performance status Escudier BJ et al. Proc ASCO 2012;Abstract CRA4502.

  35. R Study Design Period 1 Period 2 Pazopanib Sunitinib Patient preference for further treatment 1:1 N = 169 Sunitinib Pazopanib CT CT* CT * Could occur earlier if the patient crossed over early due to AE Escudier BJ et al. Proc ASCO 2012;Abstract CRA4502.

  36. Primary Endpoint: Patient Preference Primary Analysis Population 70% Percent of Patients 22% 8% With permission from Escudier BJ et al. Proc ASCO 2012;Abstract CRA4502.

  37. Which Reasons Influenced Their ChoicePrimary Analysis Population • Patients were able to select >1 option Number of Patients With permission from Escudier BJ et al. Proc ASCO 2012;Abstract CRA4502.

  38. Primary endpoint: Progression-free survival COMPARZ: A Phase III Trial of Pazopanib versus Sunitinib in Locally Advanced or Metastatic RCC R Trial Identifier: NCT00720941 Target Accrual: 927 (Closed) Pazopanib Untreated, advanced or metastatic RCC Clear cell component histology 1:1 Sunitinib www.clinicaltrials.gov. Accessed September 2012.

  39. Algorithm for Selecting Systemic Therapy

  40. For patients with asymptomatic primary RCC and symptomatic mets, do you generally recommend nephrectomy?

  41. What is your likely initial systemic treatment for RCC in a younger (age 55), otherwise healthy patient with low-volume asymptomatic mets?

  42. What is your likely initial systemic treatment for RCC in an elderly (age 78), otherwise healthy patient with low-volume asymptomatic mets?

  43. Management of Toxicities with Novel Agents

  44. A patient about to receive sunitinib asks what the chance is that the drug will need to be held or stopped due to toxicity?

  45. A patient about to receive everolimus asks what the chance is that the drug will need to be held or stopped due to toxicity?

  46. An International Expanded-Access Programme of Everolimus: Addressing Safety and Efficacy in Patients with Metastatic Renal Cell Carcinoma Who Progress After Initial Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapy Grünwald V et al. REACT Study Group. Eur J Cancer 2012;48(3):324-32.

  47. REACT: Efficacy and Safety of Everolimus • In the REACT study, safety findings and tumor responses were consistent with those observed in RECORD-1. Grünwald V et al. Eur J Cancer 2012;48(3):324-32.

More Related