Transcript GU Malignancy

ASCO G.U. 2014
Lawrence H. Einhorn
TOPICS
• Testis cancer – nothing new
• 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
Inhibition of PD-L1 by MPDL3280A<br />leads to clinical activity in<br />patients with metastatic urothelial bladder cancer (UBC)
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
326 (!!) patients
Renal Cell Cancer
Algorithm for Clear Cell RCC Therapy
Presented By Michael Atkins 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
Phase II study design
Presented By Robert Motzer at 2014 ASCO Annual Meeting
Key inclusion criteria
Presented By Robert Motzer at 2014 ASCO Annual Meeting
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
Overall survival
Presented By Robert Motzer at 2014 ASCO Annual Meeting
PROSTATE CANCER
ASCO 2004, abstracts 3 and 4<br />mCRPC
2 months improvement in OS
<br /><br />E3805<br />CHAARTED: ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in 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.
N=790
Primary endpoint: Overall survival
13.6 months
Secondary Endpoints
Presented By Christopher Sweeney at 2014 ASCO Annual Meeting
Drugs that prolong OS for CRPC
Presented By Michael Morris at 2014 ASCO Annual Meeting
PREVAIL– Study Design
Men with Metastatic
Castration
Resistant Prostate
Cancer
Chemo-naïve
N= 1717
Co-Primary Endpoint:
Radiographic PFS
Overall Survival
Enzalutamide
N=872
Placebo
N=845
PREVAIL Was Halted at the Interim Analysis for Significant Benefit with Enzalutamide
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
Enzalutamide Reduced Risk of Death by 29%
Presented By Andrew Armstrong at 2014 ASCO Annual Meeting
Enzalutamide Delayed Time to PSA Progression
Presented By Andrew Armstrong at 2014 ASCO Annual Meeting
SUMMARY
• Testis cancer
• Bladder cancer
• Renal cell cancer
• Castrate resistant prostate
cancer