Real World Practice: Adjuvant Therapy Ready for Prime Time? (Con)

Transcription

1 Real World Practice: Adjuvant Therapy Ready for Prime Time? (Con) Sumanta Kumar Pal, M.D. Associate Professor, Department of Medical Oncology Co-Director, Kidney Cancer Program City of Hope Comprehensive Cancer Center Duarte, California (USA) April 21, 2017

2 Why we are not ready for adjuvant therapy (in 10 minutes or less) Time Rationale 3 minutes Conflicting Data from ASSURE and S-TRAC 3 minutes Review of EAU Guidelines Statement 3 minutes The Horizon: Adjuvant Immunotherapy 1 minute Conclusions

3 Why we are not ready for adjuvant therapy (in 10 minutes or less) Time Rationale 3 minutes Conflicting Data from ASSURE and S-TRAC 3 minutes Review of EAU Guidelines Statement 3 minutes The Horizon: Adjuvant Immunotherapy 1 minute Conclusions

4 Conflicting Data from ASSURE and S-TRAC DFS from ASSURE 1 death on sorafenib Infectious colitis 4 deaths on sunitinib Neurologic sequelae Pulmonary embolism Gastric perforation Disease progression Haas NB et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet May 14;387(10032):

5 Conflicting Data from ASSURE and S-TRAC OS from ASSURE 1 death on sorafenib Infectious colitis 4 deaths on sunitinib Neurologic sequelae Pulmonary embolism Gastric perforation Disease progression Haas NB et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet May 14;387(10032):

6 Conflicting Data from ASSURE and S-TRAC DFS from S-TRAC No deaths attributed to treatment (5 deaths on each arm) Ravaud A et al. Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy. The New England journal of medicine Dec 08;375(23):

7 Conflicting Data from ASSURE and S-TRAC DFS from S-TRAC No deaths attributed to treatment (5 deaths on each arm) Ravaud A et al. Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy. The New England journal of medicine Dec 08;375(23):

8 Conflicting Data from ASSURE and S-TRAC OS from S-TRAC No deaths attributed to treatment (5 deaths on each arm) Ravaud A et al. Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy. The New England journal of medicine Dec 08;375(23):

9 Conflicting Data from ASSURE and S-TRAC Could central review explain the discordances? Analysis (DFS) Sunitinib Placebo Difference All patients (Central) All patients (Investigator) Would central review in ASSURE widen or narrow the difference in DFS? Ravaud A et al. Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy. The New England journal of medicine Dec 08;375(23):

10 Conflicting Data from ASSURE and S-TRAC Could central review explain the discordances? Could patient characteristics (esp. risk) explain the discordances? Haas NB et al. Adjuvant Treatment for High-Risk Clear Cell Renal Cancer: Updated Results of a High-Risk Subset of the ASSURE Randomized Trial. JAMA Oncol Mar 09.

11 Conflicting Data from ASSURE and S-TRAC Could central review explain the discordances? Could patient characteristics (esp. risk) explain the discordances? Haas NB et al. Adjuvant Treatment for High-Risk Clear Cell Renal Cancer: Updated Results of a High-Risk Subset of the ASSURE Randomized Trial. JAMA Oncol Mar 09.

12 Conflicting Data from ASSURE and S-TRAC Could central review explain the discordances? Could patient characteristics (esp. risk) explain the discordances? Could dose intensity affect outcome? Haas NB et al. Adjuvant Treatment for High-Risk Clear Cell Renal Cancer: Updated Results of a High-Risk Subset of the ASSURE Randomized Trial. JAMA Oncol Mar 09.

13 PROTECT: The Tie-Breaker? Favors Adjuvant Therapy Favors Observation

14 Why we are not ready for adjuvant therapy (in 10 minutes or less) Time Rationale 3 minutes Conflicting Data from ASSURE and S-TRAC 3 minutes Review of EAU Guidelines Statement 3 minutes The Horizon: Adjuvant Immunotherapy 1 minute Conclusions

15 EAU Guidelines on Adjuvant Therapy for RCC Bex A, Albiges L, Ljungberg B, Bensalah K, Dabestani S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Lam TB, Marconi L, Merseburger AS, Staehler M, Volpe A, Powles T. Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma. Eur Urol May;71(5):

16 EAU Guidelines on Adjuvant Therapy for RCC IKCC Network Poll (N=22) After surgery for kidney cancer, if your doctor told you that you are at high risk for recurrence (spread), would you consider taking sunitinib for 1 year in the hope that you could delay the onset of recurrence even if your overall survival was not improved? Bex A, Albiges L, Ljungberg B, Bensalah K, Dabestani S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Lam TB, Marconi L, Merseburger AS, Staehler M, Volpe A, Powles T. Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma. Eur Urol May;71(5):

17 EAU Guidelines on Adjuvant Therapy for RCC EAU Panel Members Which results from S-TRAC would change your standard practice in the context of data available in ASSURE and toxicity profiles consistent with those seen for sunitinib? Bex A, Albiges L, Ljungberg B, Bensalah K, Dabestani S, Giles RH, Hofmann F, Hora M, Kuczyk MA, Lam TB, Marconi L, Merseburger AS, Staehler M, Volpe A, Powles T. Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma. Eur Urol May;71(5):

18 Why we are not ready for adjuvant therapy (in 10 minutes or less) Time Rationale 3 minutes Conflicting Data from ASSURE and S-TRAC 3 minutes Review of EAU Guidelines Statement 3 minutes The Horizon: Adjuvant Immunotherapy 1 minute Conclusions

19 The Horizon: Adjuvant Immunotherapy IO offers the possibility of protracted survival McDermott DF et al. Long-term overall survival (OS) with nivolumab in previously treated patients with advanced renal cell carcinoma (arcc) from phase I and II studies. J Clin Oncol ;34(suppl):abstr 4507.

20 The Horizon: Adjuvant Immunotherapy IO offers the possibility of protracted survival < 10% discontinuation due to AEs Few latent toxicities? Toxicity profile more tenable in adjuvant setting? McDermott DF et al. Long-term overall survival (OS) with nivolumab in previously treated patients with advanced renal cell carcinoma (arcc) from phase I and II studies. J Clin Oncol ;34(suppl):abstr 4507.

21 The Horizon: Adjuvant Immunotherapy ECOG Adjuvant Study (PIs: Harshman, Allaf) Slide courtesy of L. Harshman, MD

22 The Horizon: Adjuvant Immunotherapy Enrolling now in Europe; needs your support!

23 The Horizon: Adjuvant Immunotherapy Study launching in Q Slide courtesy of T. Choueiri, MD

24 The Horizon: Adjuvant Immunotherapy Renal Cell Carcinoma Surgery Nivolumab Placebo Ipilimumab Details forthcoming Toxicity/Cost? Personal communication: R. Motzer, MD

25 Why we are not ready for adjuvant therapy (in 10 minutes or less) Time Rationale 3 minutes Conflicting Data from ASSURE and S-TRAC 3 minutes Review of EAU Guidelines Statement 3 minutes The Horizon: Adjuvant Immunotherapy 1 minute Conclusions

26 Why we are not ready for adjuvant therapy (in 10 minutes or less) Time Rationale 3 minutes Conflicting Data from ASSURE and S-TRAC (but the net result favors observation, especially considering PROTECT!) 3 minutes Review of EAU Guidelines Statement 3 minutes The Horizon: Adjuvant Immunotherapy 1 minute Conclusions

27 Why we are not ready for adjuvant therapy (in 10 minutes or less) Time Rationale 3 minutes 3 minutes Conflicting Data from ASSURE and S-TRAC (but the net result favors observation, especially considering PROTECT!) Review of EAU Guidelines Statement: Many patients and oncologists want more from adjuvant therapy than modest DFS benefit 3 minutes The Horizon: Adjuvant Immunotherapy 1 minute Conclusions

28 Why we are not ready for adjuvant therapy (in 10 minutes or less) Time Rationale 3 minutes 3 minutes 3 minutes Conflicting Data from ASSURE and S-TRAC (but the net result favors observation, especially considering PROTECT!) Review of EAU Guidelines Statement: Many patients and oncologists want more from adjuvant therapy than modest DFS benefit The Horizon: Adjuvant Immunotherapy It s coming; please consider current studies! 1 minute Conclusions

29 Why we are not ready for adjuvant therapy (in 10 minutes or less) Time Rationale 3 minutes 3 minutes 3 minutes Conflicting Data from ASSURE and S-TRAC (but the net result favors observation, especially considering PROTECT!) Review of EAU Guidelines Statement: Many patients and oncologists want more from adjuvant therapy than modest DFS benefit The Horizon: Adjuvant Immunotherapy It s coming; please consider current studies! 1 minute Thank you!

30 Acknowledgements Collaborators Toni Choueiri, MD Jose Karam, MD Siraj Ali, MD, PhD Axel Bex, MD Brian Rini, MD Laurence Albiges, MD Rob Uzzo, MD COH Scientific Collaborators Marcin Kortylewski, PhD Jeremy Jones, PhD Xueli Liu, PhD Kidney Cancer Association