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

Men with Metastatic Hormone Sensitive

Prostate Cancer

ADT + Docetaxel x 6 cycles

ADT Alone

ADT allowed up to 120 days prior to randomizationNo Intermittent ADT allowed

Primary Endpoint: Overall SurvivalSecondary Endpoints: PSA response rate, Time to progression, Toxicity QOL.

Primary endpoint: Overall survival

N=790

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

EnzalutamideN=872

PlaceboN=845

Co-Primary Endpoint: Radiographic PFS Overall Survival

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