Will All Adjuvant Therapy Trials Be Negative in RCC?

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2 Will All Adjuvant Therapy Trials Be Negative in RCC? Tim Eisen Eleventh European International Kidney Cancer Symposium April 2016 Crowne Plaza Barcelona Fira Center, Barcelona, Spain

3 Tim Eisen - Disclosures Company Employment Research Support Advisory Board Trial Management Group Honoraria Astra Zeneca Astellas + + Aveo Bayer GSK Immatics + Pfizer Roche + + Eleventh European International Kidney Cancer Symposium April 2016 Crowne Plaza Barcelona Fira Center, Barcelona, Spain

4 Eleventh European International Kidney Cancer Symposium April 2016 Crowne Plaza Barcelona Fira Center, Barcelona, Spain VEGFR targeting effects Multi-targeted agents

5 ARISER (G250 v Placebo) Metastases at baseline in 11% Median DFS 71 months 5 year OS 78% Risk Group Staging % of total Leibovich Score 1 T3/4; N0/X; M0 75% Any T; N+; M0 8% T1b/2; N0/NX; M0; G>3 17% 3-8 Belldegrun et al., ASCO 2013 Eleventh European International Kidney Cancer Symposium April 2016 Crowne Plaza Barcelona Fira Center, Barcelona, Spain

6 Phase III Adjuvant Trials of TKI or mtori in RCC Trial N Risk Histology Regimen ASSURE 1923 High / Inter. CC & Non-CC 1yr Sor v Sun v Plac SORCE 1704 High / Inter. CC & Non-CC 1yr or 3yr Sor v Plac S-TRAC 720 High CC 1 yr Sun v Plac PROTECT 1500 High / Inter. CC 1 yr Paz v Plac ATLAS 700 High / Inter. CC 1 yr Axi v Plac EVEREST 1170 High / Inter. CC & Non-CC 1 yr Evero v Plac Eleventh European International Kidney Cancer Symposium April 2016 Crowne Plaza Barcelona Fira Center, Barcelona, Spain

7 Disease-Free Survival Proportion Alive and Disease-Free Event s Patient s 5-yr DFS 97.5% CI HR 97.5% CI Sunitinib % % Sorafenib % % Placebo % % Sunitinib Sorafenib Placebo Median 5.8 yrs Median 5.8 yrs Median 6.0 yrs Time (Months) Presented by: Naomi B. Haas, MD

8 DFS for Clear Cell Population Proportion Alive and Disease-Free Event s Patient s 5-yr DFS 97.5% CI HR 97.5% CI Sunitinib % % Sorafenib % % Placebo % % Time (Months) Median 5.6 yrs Median 5.1 yrs Median 5.7 yrs Sunitinib Sorafenib Placebo Presented by: Naomi B. Haas, MD

9 Overall Survival Proportion Alive Sunitinib Sorafenib Placebo Events Patients 5-yr OS 97.5% CI HR 97.5% CI Sunitinib % % Sorafenib % % Placebo % % Time (Months) Presented by: Naomi B. Haas, MD

10 Overall Survival Proportion Alive Sunitinib Sorafenib Placebo Events Patients 5-yr OS 97.5% CI HR 97.5% CI Sunitinib % % Sorafenib % % Placebo % % Time (Months) Presented by: Naomi B. Haas, MD

11 Sunitinib vs Placebo Group HR 97.5% CI All Patients 1.01 (0.83, 1.23) Age <=56 Age > 56 Male Female White Non-Hispanic Other Race/Ethnicity Int Hi Risk Very High Risk AJCC Stage I - II AJCC Stage III - IV Pre-Surgery PS=0 Pre-Surgery PS>0 Clear Cell Other Histology Start Full Dose Start Reduced Dose (0.79, 1.44) (0.73, 1.25) (0.75, 1.19) (0.83, 1.81) (0.86, 1.34) (0.41, 1.28) (0.75, 1.39) (0.79, 1.30) (0.68, 1.55) (0.80, 1.25) (0.77, 1.20) (0.82, 1.98) (0.81, 1.26) (0.65, 1.63) (0.74, 1.17) (0.78, 1.73) Favors Sunitinib Favors Placebo Presented by: Naomi B. Haas, MD

12 Sorafenib vs Placebo Group All Patients Age <=56 Age > 56 Male Female White Non-Hispanic Other Race/Ethnicity Int Hi Risk Very High Risk AJCC Stage I - II AJCC Stage III - IV Pre-Surgery PS=0 Pre-Surgery PS>0 Clear Cell Other Histology Start Full Dose Start Reduced Dose HR % CI (0.81, 1.19) (0.78, 1.38) (0.73, 1.26) (0.71, 1.12) (0.90, 1.95) (0.85, 1.32) (0.29, 0.90) (0.73, 1.35) (0.76, 1.24) (0.90, 1.93) (0.71, 1.12) (0.78, 1.22) (0.75, 1.84) (0.81, 1.24) (0.58, 1.46) (0.68, 1.08) (0.96, 2.02) Favors Sorafenib Favors Placebo Presented by: Naomi B. Haas, MD

13 Phase III Adjuvant Trials of TKI or mtori in RCC Trial N Risk Histology Regimen ASSURE 1923 High / Inter. CC & Non-CC 1yr Sor v Sun v Plac SORCE 1704 High / Inter. CC & Non-CC 1yr or 3yr Sor v Plac S-TRAC 720 High CC 1 yr Sun v Plac PROTECT 1500 High / Inter. CC 1 yr Paz v Plac ATLAS 700 High / Inter. CC 1 yr Axi v Plac EVEREST 1170 High / Inter. CC & Non-CC 1 yr Evero v Plac Eleventh European International Kidney Cancer Symposium April 2016 Crowne Plaza Barcelona Fira Center, Barcelona, Spain

14 Phase III Adjuvant Trials of TKI or mtori in RCC Trial N Risk Histology Regimen ASSURE 1923 High / Inter. CC & Non-CC 1yr Sor v Sun v Plac SORCE 1704 High / Inter. CC & Non-CC 1yr or 3yr D Sor v Plac S-TRAC 720 High CC 1 Dyr Sun v Plac PROTECT 1500 High / Inter. CC 1 yr Paz v Plac ATLAS 700 High / Inter. CC 1 yr Axi v Plac EVEREST 1170 High / Inter. CC & Non-CC 1 yr Evero v Plac Eleventh European International Kidney Cancer Symposium April 2016 Crowne Plaza Barcelona Fira Center, Barcelona, Spain

15 Disease-Free Survival Proportion Alive and Disease-Free Event s Patient s 5-yr DFS 97.5% CI HR 97.5% CI Sunitinib % % Sorafenib % % Placebo % % Sunitinib Sorafenib Placebo Median 5.8 yrs Median 5.8 yrs Median 6.0 yrs Time (Months) Presented by: Naomi B. Haas, MD

16 AVANT study design FOLFOX4 (24 weeks) Resected colon cancer (high-risk stage II and stage III) (n=3450) FOLFOX4 (24 weeks) Bevacizumab 5 mg/kg q2w with chemotherapy and 7.5 mg/kg q3w monotherapy (48 weeks) XELOX4 (24 weeks) Bevacizumab 7.5 mg/kg q3w (48 weeks) Primary endpoint: DFS Secondary endpoints: OS, safety De Gramont A et al. Lancet Oncology 2012.

17 Disease-free survival in AVANT Disease-free survival at 1 year Disease-free survival at 3 years FOLFOX4 + bevacizumab XELOX + bevacizumab Favours bevacizumab addition Favours chemo only Favours bevacizumab addition Favours chemo only De Gramont A et al. Lancet Oncol 2012.

18 Disease-Free Survival Proportion Alive and Disease-Free ?? 3 years sorafenib in SORCE?? Event s Patient s 5-yr DFS 97.5% CI HR 97.5% CI Sunitinib % % Sorafenib % % Placebo % % Sunitinib Sorafenib Placebo Median 5.8 yrs Median 5.8 yrs Median 6.0 yrs Time (Months) Presented by: Naomi B. Haas, MD

19 Will All Adjuvant Therapy Trials Be Negative in RCC? Trials investigating TKI for 1 year are likely to be negative Possible to envisage a role for short term in high risk group EVEREST outcome is completely unknown Sorafenib for 3 years in SORCE remains an important question Eleventh European International Kidney Cancer Symposium April 2016 Crowne Plaza Barcelona Fira Center, Barcelona, Spain

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