1. ASCO G.U. 2014
Lawrence H. Einhorn

2. TOPICS Testis cancer – nothing new Bladder cancer Renal cell cancer
July 1, 2014 JCO (correspondence) – Albany and Einhorn: Pitfalls in low level elevations of AFP
Bladder cancer
PD-L1
Renal cell cancer
Ranking of treatment options
Nivolumab PD-1
Prostate cancer
Adjuvant Docetaxel
Enzalutamide

3. Inhibition of PD-L1 by MPDL3280A<br />leads to clinical activity in<br />patients with metastatic urothelial bladder cancer (UBC)

4. MPDL 3280A PD-L1 I IN METASTATIC BLADDER CA
65 patients entered
71% received 2 or more prior therapies
17 of 65 (26%) response rate, but 13 of 30 (43%) if PD-L1 positive (2+ or 3+) by IHC, including 2 C.R.s
Genentech phase II study to enroll (!!) patients

5. Renal Cell Cancer

6. Algorithm for Clear Cell RCC Therapy
Presented By Michael Atkins at 2014 ASCO Annual Meeting

7. Presented By Robert Motzer at 2014 ASCO Annual Meeting
Nivolumab for metastatic renal cell <br />carcinoma (mRCC): results of a randomized, dose-ranging phase II trial
Presented By Robert Motzer at 2014 ASCO Annual Meeting

8. Presented By Robert Motzer at 2014 ASCO Annual Meeting
Phase II study design
Presented By Robert Motzer at 2014 ASCO Annual Meeting

9. Key inclusion criteria
Presented By Robert Motzer at 2014 ASCO Annual Meeting

10. NIVOLUMAB IN METASTATIC RENAL CELL CA
168 patients entered; all received prior therapy and 70% 2 or more including VEGF TKIs (98%) MTOR inhibitors (38%) and immunotherapy (24%)
35 of 168 (21%) response rate; 19 of these 35 (54%) remissions were 12+ month duration

11. Presented By Robert Motzer at 2014 ASCO Annual Meeting
Overall survival
Presented By Robert Motzer at 2014 ASCO Annual Meeting

12. PROSTATE CANCER

13. ASCO 2004, abstracts 3 and 4<br />mCRPC
2 months improvement in OS

14. <br /><br />E3805<br />CHAARTED: ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer

15. Men with Metastatic Hormone Sensitive Prostate Cancer
E3805 – CHAARTED Treatment
ADT +
Docetaxel x 6 cycles
Men with Metastatic Hormone Sensitive Prostate Cancer
ADT Alone
ADT allowed up to 120 days prior to randomization
No Intermittent ADT allowed
Primary Endpoint: Overall Survival
Secondary Endpoints:
PSA response rate,
Time to progression,
Toxicity
QOL.

16. Primary endpoint: Overall survival
13.6 months
Primary endpoint: Overall survival

17. Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
Secondary Endpoints
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting

18. Drugs that prolong OS for CRPC
Presented By Michael Morris at 2014 ASCO Annual Meeting

19. Men with Metastatic Castration Resistant Prostate Cancer
PREVAIL– Study Design
Enzalutamide
N=872
Men with Metastatic Castration Resistant Prostate Cancer
Chemo-naïve
N= 1717
Placebo
N=845
Co-Primary Endpoint:
Radiographic PFS
Overall Survival

20. Presented By Andrew Armstrong at 2014 ASCO Annual Meeting
PREVAIL Was Halted at the Interim Analysis for Significant Benefit with Enzalutamide
Presented By Andrew Armstrong at 2014 ASCO Annual Meeting

21. Presented By Andrew Armstrong at 2014 ASCO Annual Meeting
Enzalutamide Prolonged Radiographic <br />Progression-Free Survival
Presented By Andrew Armstrong at 2014 ASCO Annual Meeting

22. Enzalutamide Reduced Risk of Death by 29%
Presented By Andrew Armstrong at 2014 ASCO Annual Meeting

23. Enzalutamide Delayed Time to PSA Progression
Presented By Andrew Armstrong at 2014 ASCO Annual Meeting

25. SUMMARY
Testis cancer
Bladder cancer
Renal cell cancer
Castrate resistant prostate cancer