ASCO G.U. 2014 Lawrence H. Einhorn

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

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

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

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

Presented By Robert Motzer at 2014 ASCO Annual Meeting 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

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.

Primary endpoint: Overall survival 13.6 months Primary endpoint: Overall survival

Presented By Christopher Sweeney at 2014 ASCO Annual Meeting 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

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

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

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