Atezolizumab Adjuvant Study: Medical Oncologist Perspective. Sumanta K. Pal, MD City of Hope Comprehensive Cancer Center

Transcription

1 Atezolizumab Adjuvant Study: Medical Oncologist Perspective Sumanta K. Pal, MD City of Hope Comprehensive Cancer Center

2 Trial overview Key issues Outline Challenges with neoadjuvant therapy Placebo control vs observation Referral patterns

3 Trial Design: Schema Objectives: Characterize the efficacy of atezolizumab vs placebo in patients with high risk RCC post-nephrectomy or complete metastastectomy (Primary Endpoint: Investigator-assessed DFS) Key Eligibility (N=664) High risk OR limited metastasis s/p metastasectomy s/p nephrectomy 12 weeks No evidence of residual disease clear cell or sarcomatoid histology Stratification Factors Disease stage (T2/T3a vs. T3b/c/T4/N+ vs metastasectomy) PD-L1 (IC0 vs IC1/2/3) Region (US/Canada vs ROW) 1:1 Randomization Placebo IV q3w x 16 cycles Atezolizumab 1200 mg IV q3 wk x 16 cycles

4 Trial Design: Eligibility Histologically confirmed RCC (clear cell or sarcomatoid) Fully resected localized disease T2, grade 4 T3a, grade 3-4 T3b/c, any grade T4, any grade TxN+ any grade or Fully resected metastatic disease Representative tissues for PD-L1 assessment prior to enrollment

5 Trial Design: Objectives/Endpoints Secondary objectives Overall survival Disease-free survival in patients with IC 1/2/3 Disease-specific survival Distant metastasis-free survival 3-year DFS rate Incidence, nature and severity of adverse events

6 Trial Design: Objectives/Endpoints Correlative studies PD-L1 expression T-effector signatures in archival tumor tissues QOL measures FKSI-19 EQ-5D-DL Surgical complication rates

7 Trial Design: Comparison Renal Cell Carcinoma Surgery Immunotherapy Placebo What is true benefit of neoadjuvant? Immunotherapy Surgery Immunotherapy Renal Cell Carcinoma Surgery Observation Will observed patients more readily transition to systemic therapy?

8 Lessons Learned: Melanoma Stage III Melanoma Surgery Ipilimumab Placebo Is neoadjuvant therapy necessary? Eggermont A et al New England Journal of Medicine. 2016

9 Lessons Learned: Bladder Cancer Data for neoadjuvant therapy exists in bladder cancer Medical Oncology Urology Will urologists and medical oncologists collaborate? Bergerot et al J Clin Oncol 34, 2016 (suppl; abstr 4540)

10 Lessons Learned: Bladder Cancer Risk of surgical complications Too toxic for the surgical patient Adjuvant therapy better selects patients Prolonged diagnosis and referral Marginal benefit Delay in surgery Age and comorbidities Significant concerns re: neoadjuvant chemo (Survey of 132 SUO members) 0% 10% 20% 30% 40% 50% 60% Cowan NG et al Adv Urol 2014

11 Lessons Learned: Preoperative Studies in RCC Author Treatment Patients Undergoing Surgery Powles et al (JAMA Oncol 2016) Pazopanib x wks Stage IV (N=104) 63 (61%) Jonasch et al (JCO 2009) Bevacizumab +/- Erlotinib x 8 wks Stage IV (N=52) 42 (81%) Powles et al (Eur Urol 2011) Sunitinib x wks Stage IV (N=66) 47 (71%) Rini et al (J Urol 2012) Sunitinib x 18 wks Stage I-IV (N M0 =19) (N M1 =11) 13 (43%) Karam et al (ASCO 2013) Axitinib x 12 wks Stage II-III (N=24) 24 (100%)

12 International Tumor Board Heng Powles Srinivas Escudier Lara Motzer Figlin Vogelzang Tannir Jonasch Hutson Rini Choueiri

13 Which studies have you participated in? Heng Srinivas SORCE 13% S-TRAC 6% EVEREST 19% ATLAS 6% PROTECT 44% Powles Escudier ASSURE 12% Lara Motzer Figlin Vogelzang Tannir Jonasch Hutson Rini Choueiri

14 Is Placebo Control Permissible? Either, 7% Heng Powles No, 28% Srinivas Yes, 64% Escudier Lara Motzer Figlin Vogelzang Tannir Jonasch Hutson Rini Choueiri

15 Is Placebo Control Permissible? Heng Placebo control is always important in randomized trials that have DFS or RFS for end point Powles Srinivas Not for pts with S-TRAC eligibility Escudier Lara Motzer Figlin Vogelzang Tannir Jonasch Hutson Rini Choueiri

16 Lessons Learned: Adjuvant RCC Internal (Pre-nephrectomy) Internal (Post-nephrectomy) External (Post-nephrectomy) 0 EVEREST Accruals Source: Internal data, City of Hope Genitourinary Cancers Program

17 Distribution of referrals? Heng Powles Srinivas Escudier Lara Motzer Figlin Vogelzang Tannir Jonasch Hutson Rini Choueiri

18 Distribution of referrals? Heng Srinivas 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Internal (Pre-Nephrectomy) Internal (Post-Nephrectomy) External (Post-Nephrectomy) Powles Escudier Lara Motzer Figlin Vogelzang Tannir Jonasch Hutson Rini Choueiri

19 Key Points The clinical benefit of neoadjuvant therapy may remain unknown Both observation and placebo controls have unique issues Traditionally the paradigm of neoadjuvant therapy in GU oncology has been adopted slowly Acquisition of appropriate referrals for neoadjuvant therapy may be a challenge

20 Thank You! Gregg Fine, MD Christina Schiff, MD Herschel Wallen, MD Robert Uzzo, MD Brian Rini, MD Axel Bex, MD Christina Suarez, MD Laurence Albiges, MD