1. Please note, these are the actual video-recorded proceedings from the live CME event and may include the use of trade names and other raw, unedited content. Select slides from the original presentation are omitted where Research To Practice was unable to obtain permission from the publication source and/or author. Links to view the actual reference materials have been provided for your use in place of any omitted slides.

2. YEAR IN REVIEW 2012: GU David I Quinn, MBBS, PhD Medical Director, Norris Cancer Hospital and Clinics Leader, Developmental Therapeutics Head, GU Cancer Section Division of Cancer Medicine and Blood Diseases USC/Norris Comprehensive Cancer Center

3. Cabozantinib has resulted in bone scan and symptom improvements in prostate cancer but no other solid tumor.

4. Which agent are you most likely to recommend for a patient with asymptomatic metastatic prostate cancer progressing on androgen deprivation?

5. To what extent does radium-223 chloride cause myelosuppression?

6. Updated Analysis of the Phase III, Double-Blind, Randomized, Multinational Study of Radium ‑ 223 Chloride in Castration-Resistant Prostate Cancer (CRPC) Patients with Bone Metastases (ALSYMPCA) Proc ASCO 2012;Abstract LBA 4512 C. Parker, S. Nilsson, D. Heinrich, J.M. O’Sullivan, S. Fosså, A. Chodacki, P. Wiechno, J. Logue, M. Seke, A. Widmark, D.C. Johannessen, P. Hoskin, D. Bottomley, R. Coleman, N. Vogelzang, C.G. O’Bryan-Tear, J. Garcia-Vargas, M. Shan, and O. Sartor

7. Radium-223 Targets Bone Metastases Alpha-particles induce double-strand DNA breaks in adjacent tumor cells 1 Short penetration of alpha emitters (2-10 cell diameters) = highly localized tumor cell killing and minimal damage to surrounding normal tissue 1. Perez et al. Principles and Practice of Radiation Oncology. 5th ed. Lippincott Williams & Wilkins; 2007:103.

8. ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) Phase III Study Design TREATMENT 6 injections at 4-week intervals Radium-223 (50 kBq/kg) + Best standard of care Placebo (saline) + Best standard of care N = 921 PATIENTS Confirmed symptomatic CRPC ≥ 2 bone metastases No known visceral metastases Post- docetaxel or unfit for docetaxel Confirmed symptomatic CRPC ≥ 2 bone metastases No known visceral metastases Post- docetaxel or unfit for docetaxel Planned follow-up is 3 years Total ALP: < 220 U/L vs ≥ 220 U/L Bisphosphonate use: Yes vs No Prior docetaxel: Yes vs No Total ALP: < 220 U/L vs ≥ 220 U/L Bisphosphonate use: Yes vs No Prior docetaxel: Yes vs No STRATIFICATION Clinicaltrials.gov identifier: NCT00699751. R A N D O M I Z E D 2:1 R A N D O M I Z E D 2:1

9. ALSYMPCA Updated Analysis: Overall Survival Radium-223, n = 614 Median OS: 14.9 months Placebo, n = 307 Median OS: 11.3 months HR = 0.695 95% CI, 0.581, 0.832 P = 0.00007 Month 036912151821242730333639 0 10 20 30 40 50 60 70 80 90 100 % With permission from Parker C et al. Proc ASCO 2012;Abstract LBA4512.

10. ESMO 2012 – Prostate ALSYMPCA: Radium-223 Chloride in mCRPC Parker C et al. Proc ESMO 2012;Abstract 898PD. –Updated analysis substantiates Ra-223 as an effective therapy that significantly improves OS and time to first SRE, with a highly favorable safety profile –Ra-223 showed significantly better preservation of QOL, with improved functioning and well-being, compared to Pbo in pts with bone metastasis

11. Increased Survival with Enzalutamide in Prostate Cancer After Chemotherapy Scher HI et al. N Engl J Med 2012;367(13):1187-97.

12. AFFIRM: Interim Analysis of Enzalutamide versus Placebo in Patients with CRPC Scher HI et al. N Engl J Med 2012;367(13):1187-97. Enzalutamide (n = 800) Placebo (n = 399) Hazard ratiop-value Overall survival18.4 mo13.6 mo0.63< 0.001 Progression- free survival*8.3 mo2.9 mo0.40< 0.001 Time to PSA progression8.3 mo3.0 mo0.25 < 0.001 PSA response rate54%2%— < 0.001 *According to radiographic evidence

13. AFFIRM: Frequent Adverse Events More Common with Enzalutamide Scher HI et al. N Engl J Med 2012;367(13):1187-97. Adverse event Enzalutamide (n = 800) Placebo (n = 399) Any gradeGrade ≥3 Any gradeGrade ≥3 Fatigue34%6%29%7% Diarrhea21%1%18%< 1% Hot flash20%0%10%0% Musculoskeletal pain14%1%10%< 1% Headache12%< 1%6%0% Seizures were reported in 5 patients (0.6%) receiving enzalutamide.

14. Interim Analysis (IA) Results of COU-AA- 302, a Randomized, Phase 3 Study of Abiraterone Acetate (AA) in Chemotherapy-Naïve Patients (pts) with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Proc ASCO 2012;Abstract LBA 4518 Charles J. Ryan, Matthew Raymond Smith, Johann Sebastian De Bono, Arturo Molina, Christopher Logothetis, Paul L. De Souza, Karim Fizazi, Paul N. Mainwaring, Jose Maria Piulats Rodriguez, Siobhan Ng, Joan Carles, Peter Mulders, Thian San Kheoh, Thomas W. Griffin, Eric Jay Small, Howard I. Scher, Dana E. Rathkopf, on behalf of the COU-AA-302 Investigators

15. Overall Study Design of COU-AA-302 Phase 3 multicenter, randomized, double-blind, placebo-controlled study conducted at 151 sites in 12 countries; USA, Europe, Australia, Canada Stratification by ECOG performance status 0 vs 1 AA 1000 mg daily Prednisone 5 mg BID (Actual n = 546) AA 1000 mg daily Prednisone 5 mg BID (Actual n = 546) Co-Primary: rPFS by central review OS Secondary: Time to opiate use (cancer-related pain) Time to initiation of chemotherapy Time to ECOG-PS deterioration TTPP Efficacy end points Placebo daily Prednisone 5 mg BID (Actual n = 542) Placebo daily Prednisone 5 mg BID (Actual n = 542) R A N D O M I Z E D 1:1 R A N D O M I Z E D 1:1 Progressive chemo- naïve mCRPC patients (Planned N = 1,088) Asymptomatic or mildly symptomatic Patients Ryan CJ et al. Proc ASCO 2012;Abstract LBA4518.

16. Statistically Significant Improvement in rPFS not OS NR, not reached; PL, placebo; rPFS, radiographic PFS. Data cutoff 12/20/2010. 100 80 60 40 20 0 0 Progression-Free (%) 369151812 546 542 489 400 340 204 164 90 12 3 0000 AA PL 46 30 Time to Progression or Death (Months) AA + P PL + P AA + P (median, mos):NR PL + P (median, mos):8.3 HR (95% CI):0.43 (0.35-0.52) P value:< 0.0001 AA + P (median, mos):NR PL + P (median, mos):27.2 HR (95% CI):0.75 (0.61-0.93) P value:0.0097 546 542 538 534 482 465 452 437 27 25 0000 524 509 503 493 0202 120 106 258 237 412 387 100 80 60 40 20 0 0 Survival (%) 3121527 Time to Death (Months) 33 AA + P PL + P 6930242118 AA PL Pre-specified significance level by O’Brien-Fleming Boundary = 0.0008. Data cutoff 12/20/2011. With permission from Ryan CJ et al. Proc ASCO 2012;Abstract LBA4518.

17. Phase III (SYNERGY) GU 68/OGX-011-11: Comparison of Standard First-Line Docetaxel/Prednisone to Docetaxel/Prednisone in Combination with Custirsen (OGX-011) in mCRPC Eligibility: Metastatic castration-resistant prostate cancer progressing while on or after androgen ablation Custirsen: Clusterin is an antiapoptotic protein that is upregulated in response to various cell-death triggers such as chemotherapy Custirsen is an oligonucleotide antisense to the mRNA for clusterin

18. First-Line Use of Cabazitaxel in Chemotherapy-Naïve Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Three-Arm Study in Comparison with Docetaxel Proc ASCO 2012;Abstract TPS4696 Stephane Oudard, Lisa Sengelov, Paul N. Mainwaring, Antoine Thiery-Vuillemin, Christine Theodore, Evgeny Kulikov, Jeffrey Yachnin, Ivo Kocak, Vesa V. Kataja, Marjaana Luukkaa, Aleander Nosov, Marie Hjelm-Eriksson, Jeffrey Bubis, Liji Shen, Marie-Laure Risse, A. Oliver Sartor

19. Phase III FIRSTANA Study (NCT01308567) Primary: OS Secondary: PCWG2 PFS rPFS by central review Tumor response (RECIST) PSA response PSA PFS Pain response Pain PFS TTP SRE QOL Efficacy end points Progressive chemo- naïve mCRPC patients (Planned N = 1,170) Stratified by: ECOG (0, 1 vs 2) Measurable Dz Region Patients CBZ = cabazitaxel; DOC = docetaxel R A N D O M I Z E D 1:1:1 R A N D O M I Z E D 1:1:1 DOC 75 mg/m 2 IV Q3W Prednisone 10 mg QD DOC 75 mg/m 2 IV Q3W Prednisone 10 mg QD CBZ 20 mg/m 2 IV Q3W Prednisone 10 mg QD CBZ 20 mg/m 2 IV Q3W Prednisone 10 mg QD CBZ 25 mg/m 2 IV Q3W Prednisone 10 mg QD CBZ 25 mg/m 2 IV Q3W Prednisone 10 mg QD Oudard S et al. Proc ASCO 2012;Abstract TPS4696.

20. CALGB-90802: Everolimus With or Without Bevacizumab in Advanced Kidney Cancer After First-Line Therapy www.clinicaltrials.gov, October 2012. Key Eligibility Criteria: Metastatic or unresectable RCC Some clear cell histology Measurable disease Treated with ≥ 1 prior VEGFR TKI and have progressed or are intolerant to treatment RANDOMIZERANDOMIZE Everolimus Everolimus + Bevacizumab N = 700 Primary Endpoint: Overall survival Secondary Endpoints: PFS, ORR, ≥ Grade 3 toxicity

21. Robert Motzer, T. E. Hutson, James Reeves, Robert Hawkins, Jun Guo, Paul Nathan, Michael Staehler, Paul de Souza, Jaime R. Merchan, Kate Fife, Jie Jin, Robert Jones, Hirotsugu Uemura, Ugo De Giorgi, Ulrika Harmenberg, Jinwan Wang, David Cella, Lauren McCann, Keith Deen, and Toni K. Choueiri Proc ESMO 2012;Abstract LBA8_PR Randomized, Open Label, Phase III Trial of Pazopanib versus Sunitinib in First-Line Treatment of Patients with Metastatic Renal Cell Carcinoma (mRCC): Results of the COMPARZ Trial

22. Pazopanib Sunitinib NMedian PFS Pazopanib5578.4 mo Sunitinib5539.5 mo HR = 1.047 With permission from Motzer R et al. Proc ESMO 2012;Abstract LBA8_PR. Months Proportion Progression-Free Primary Endpoint: Progression-Free Survival (Independent Review)

23. Hair color change Weight decreased Serum ALT increased Alopecia Upper abdominal pain Serum AST increased Fatigue Rash Pain in extremity Constipation Taste alteration LDH increased Serum creatinine increased Peripheral edema Hand-foot syndrome Dyspepsia Pyrexia Leukopenia Hypothyroidism Epistaxis Serum TSH increased Mucositis Neutropenia Anemia Thrombocytopenia Relative Risk in Adverse Events AE occurrence ≥10% in either arm; 95% CI for RR does not cross 1 Favors pazopanib Favors sunitinib    With permission from Motzer R et al. Proc ESMO 2012;Abstract LBA8_PR.