The future of our patients already treated with first line chemotherapy First of all, I would like to take this opportunity to thank the Mediterranean Multidisciplinary Oncology Forum for inviting me here to speak before you today. I am excited about this new organization and look forward to further cooperation and exploration among researchers in the Mediterranean area. Today I am going to talk about… Jose R. Germà Lluch MD PhD Institut Català of Oncology

1970 1980 1990 2000 Early reviews reported OR in 6.5% of 3184 patients Colon Cancer QMT. Metastatic & Adjuvant Breast Cancer QMT. Metastatic Lung Cancer QMT. Metastatic Lung Cancer QMT. Adjuvant Breast Cancer QMT. Adjuvant 1970 1980 1990 2000 Early reviews reported OR in 6.5% of 3184 patients Review from 26 trials published between 1987-1991: - OR 8.7% (95% CI 6.4-9.0%). - OR rate >10%: vinblastine, trimetrexate, mitoguazone & estramustine. Yagoda A. Cancer 71:1098-109, 1993. Mitoxantrone/Prednisone as the palliative standard of care. Tannock IF. J Clin Oncol 14:1756-64, 1996. Kantoff PW. J Clin Oncol 17:2506-13, 1999. Docetaxel as the standard of care in HRPC leading to superior OS and improved RR in terms of pain, serum PSA levels and QOL. Tannock IF. N Engl J Med 351:1502-12, 2004. Petrylak DP. N Engl J Med 351:1513-20, 2004.

TAX 327 SWOG 9916 increased rates of AEs. 1) It is secure. 1) Improvement in Sv at the cost of an 2) Significant Improvement of: increased rates of AEs. - Survival (18.9 vs 16.5 months). 2) Significant Improvement of: 24% risk of death reduction (p=0.009). - Survival (17.5 vs 15.6 months). - PSA response (45% vs 32%, p=0.0005). 20% risk of death reduction (p=0.02). - Pain improvement (35% vs 22%, p=0.01). - PSA response (50% vs 27%, p<0.001). - QOL (22% vs 13%, p=0.009).

116 Patients Institut Català d’Oncologia l’Hospitalet Median 23.133 (IC 95%; 17.909 – 28.358) Change hydroxyl for methoxy

Institut Català d’Oncologia l’Hospitalet 88 Patients Received Docetaxel in a 3 weekly Schedule: Mediana 26.567 (IC 95%; 19.197 – 33.936) Change hydroxyl for methoxy

Bone metastases – 63% Paliative Radiation 60% Bifosfonates Change hydroxyl for methoxy Median age – 67 yo (49 – 80) Bone metastases – 63% Paliative Radiation 60% Bifosfonates Analgesic use – 0: 35% 1: 59.8% 2: 14.5% 3: 25.8% Median OS - 26.567 (IC 95%; 19.197 – 33.936)

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Change hydroxyl for methoxy 09 / 32

CABAZITAXEL Change hydroxyl for methoxy 09 / 32

Change hydroxyl for methoxy 09 / 32

After 12-24 moths these b… become hormone independent 6 months from a aisymtomatic to become symtomatic. 02 / 32

After 12-24 moths these b… become hormone independent 6 months from a aisymtomatic to become symtomatic. 02 / 32

After 12-24 moths these b… become hormone independent 6 months from a aisymtomatic to become symtomatic. 02 / 32

These After 12-24 moths these b… become hormone independent 6 months from a aisymtomatic to become symtomatic.

These After 12-24 moths these b… become hormone independent 6 months from a aisymtomatic to become symtomatic.

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Institut Català d’Oncologia l’Hospitalet 88 Patients Received Docetaxel in a 3 weekly Schedule: Mediana 10.500 (IC 95%; 5.313 – 15.687) Second-line chemotherapy 50% Ciclofosfamide 22% Mitoxantrone 11% Docetaxel (3 wk) 11% Docetaxel (weekly) 6% Abiraterone Change hydroxyl for methoxy

Trial (Agent Approved) Year Disease State Comparator HR P value TAX327 (Docetaxel) 2004 Chemo-naïve CRPC Mitoxantrone Prednisone 0.76 (0.62-0.94) 0.009 SWOG 9916 Mitoxantrone Prednisone 0.80 (0.67-0.97) 0.02 TROPIC (Cabezitaxel) 2010 Post-Docetaxel CRPC 0.70 (0.59-0.83) <0.0001 Docetaxel 2.4 m Cabecitaxel 2.4 m ORGAN CONFINED LOCALLY ADVANCED RISING PSA HORMONE NAIVE RISING PSA ANDROGEN INDEPENDENT CLINICAL METASTASIS AI ASYMPTOMATIC CLINICAL METASTASIS AI SYMPTOMATIC 02 / 32

Trial (Agent Approved) Year Disease State Comparator HR P value IMPACT (Provenge vaccine) 2010 Chemo-naïve CRPC Placebo 0.775 (0.61-0.98) 0.032 TAX327 (Docetaxel) 2004 Chemo-naïve CRPC Mitoxantrone Prednisone 0.76 (0.62-0.94) 0.009 TROPIC (Cabezitaxel) Post-Docetaxel 0.70 (0.59-0.83) <0.0001 COU-AA-301 (Abiraterone) 0.64 (0.54-0.77) Sipuleucel-T 4.1 m Docetaxel 2.4 m Cabezitaxel 2.4 m Abiraterone 3.9 m ORGAN CONFINED LOCALLY ADVANCED RISING PSA HORMONE NAIVE RISING PSA ANDROGEN INDEPENDENT CLINICAL METASTASIS AI ASYMPTOMATIC CLINICAL METASTASIS AI SYMPTOMATIC 02 / 32

MDV3100 MDV3100 PROSTVAC IPILIMUMAB Sipuleucel-T 4.1 m Docetaxel 2.4 m Cabezitaxel 2.4 m Abiraterone 3.9 m COMBINATIONS DENOSUMAB ORGAN CONFINED LOCALLY ADVANCED RISING PSA HORMONE NAIVE RISING PSA ANDROGEN INDEPENDENT CLINICAL METASTASIS AI ASYMPTOMATIC CLINICAL METASTASIS AI SYMPTOMATIC Abiraterone 02 / 32

Thank you for your attention. jrgema@iconcologia.net Gran Via, s/n km 2,7 08907 L'Hospitalet - Barcelona Tels. 93 335 70 11 / 90 11 Fax 93 260 77 83 http://www.iconcologia.net Hank you for your attention