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“Taking Care of Tomorrows Patient Better than Today”… the Future is Now David O’Malley, M.D.

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Presentation on theme: "“Taking Care of Tomorrows Patient Better than Today”… the Future is Now David O’Malley, M.D."— Presentation transcript:

1 “Taking Care of Tomorrows Patient Better than Today”… the Future is Now David O’Malley, M.D.

2 Describe the Collaborative Trials (GOG) –Past –Present –Future Discuss Ovarian Cancer Research at The James Cancer Center – OSU

3 Have we made improvements? Are we doing any good? Salani, et al. Overview of epithelial ovarian cancer and updates in management strategies, Expert Rev. Obstet. Gynecol. (2009)

4 Ovarian Carcinoma - Talking the same language Symptoms Diagnosis Chemotherapy # 1 Progression Chemo #2 Chemo #3+ SupportiveCare Death Consolidation Cure Staging Primary cytoreduction Interval Cytoreduction Cytoreduction SecondaryCytoreduction

5 Gynecologic Oncology Group (GOG) Adjuvant/First Line Therapy –GOG 218 (NEJM just published) –GOG 252 (just completed enrollment) –GOG 262 (just completed enrollment) Recurrent Therapy –GOG 213 (just completed enrollment, except for surgery question

6 GOG 218 Study Scheme Bevacizumab during Treatment and as Maintenance Burger RA, NEJM 2012 Previously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancer Stage III optimal (macroscopic) Stage III suboptimal Stage IV RANDOMIZERANDOMIZE Experimental arm: Carboplatin AUC 6 IV d 1 Paclitaxel 175 mg/m 2 IV d 1 Bevacizumab 15 mg/kg d1 Control arm: Carboplatin AUC 6 Carboplatin AUC 6 d1 Paclitaxel 175 mg/m 2 Paclitaxel 175 mg/m 2 d1 Placebo d1 Every 21 days x 6 courses n = 1873 Placebo x 16 cycles Maintenance Bevacizumab every 3 wks for 16 cycles Experimental arm: Carboplatin AUC 6 IV d 1 Paclitaxel 175 mg/m 2 IV d 1 Bevacizumab 15 mg/kg d1

7 02468101214 16182022242628 30323436 Arm I CP + PLA → PLA (n=625) Arm II CP + BEV → PLA (n=625) Arm III CP + BEV →  BEV (n=623) Patients with event, n (%) 375(60)405(67)363(71) Median PFS, months 10.411.513.9 HR (stratified) (95% CI) 0.864 (0.759–0.996) 0.726 (0.627–0.840) One-sided log-rank p-value 0.0218*<0.0001 a 218 Progression Free Survival Proportion surviving progression free Months since randomization 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Median follow-up: 17.4 months Burger RA, J Clin Oncol 2010;28(18S):

8 GOG 252 IV versus IP (different regimens) Bevacizumab during Treatment and as Maintenance GOG Statistical Manual Previously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancer Stage II. III optimal Stage III suboptimal (some) Stage IV (some) RANDOMIZERANDOMIZE Paclitaxel 135 mg/m2 IV on day 1 Cisplatin 75 mg/m2 IP on day 2 Paclitaxel 60 mg/m2 IP on day 8 Bevacizumab 15 mg/kg IV on day 1 beginning on cycle 2 Paclitaxel 80 mg/m2 IV days 1, 8, 15 Carboplatin AUC 6 IV day 1 Bevacizumab 15 mg/kg IV on day 1 beginning on cycle 2 Paclitaxel 80 mg/m2 IV days 1, 8, 15 Carboplatin AUC 6 IP day 1 Bevacizumab 15 mg/kg IV on day 1 beginning on cycle 2 Maintenance Bevacizumab x 16 cycles

9 GOG 262 Different taxol IV schedules *OPTIONAL Bevacizumab during Treatment and as Maintenance GOG Statistical Manual Previously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancer Stage II. III optimal suboptimal Stage IV RANDOMIZERANDOMIZE Paclitaxel 80 mg/m2 IV days 1, 8,15 Carboplatin AUC 6 IV day 1 *Bevacizumab 15 mg/kg IV on day 1 Paclitaxel 175 mg/m2 IV days 1 Carboplatin AUC 6 IV day 1 *Bevacizumab 15 mg/kg IV on day 1 Maintenance* OPTIONAL Bevacizumab until PROGRESSION

10 TRINOVA - 3 (AMG 386) Anti VEGF and angiopoietin agent TRINOVA 3 AMGEN PROTOCOL Previously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancer Post operative Stage III, IV Post operative Stage III, IV Neoadjuvant Neoadjuvant RANDOMIZERANDOMIZE Experimental arm: Carboplatin AUC 5-6 IV d 1 Paclitaxel 175 mg/m 2 IV d 1 AMG 386 weekly Control arm: Carboplatin AUC 5-6 Carboplatin AUC 5-6 d1 Paclitaxel 175 mg/m 2 Paclitaxel 175 mg/m 2 d1 Placebo weekly n = 2000 Weekly Placebo x 18 months Maintenance AMG 386 x 18 months 2:1 randomization

11 NEXT STEP in GOG PARP inhibitors GOG Statistical Manual Previously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancer Stage II. III optimal Stage III suboptimal Stage IV NEOADJUVANT? RANDOMIZERANDOMIZE Paclitaxel Carboplatin PARP Paclitaxel Carboplatin PLACEBO Paclitaxel Carboplatin PARP Maintenance PLACEBO Paclitaxel Carboplatin PLACEBO PARP

12 Recurrent Cancer

13 GOG 213 Bev with treatment UNTIL PROGRESSION Plus Surgery question GOG Statistical Manual Recurrent Ovarian Cancer in patients with a treatment free interval for at least 6 months from primary therapy RANDOMIZERANDOMIZE Paclitaxel IV Carboplatin IV Surgery Maintenance Surgical candidate? No Yes RANDOMIZERANDOMIZE No Surgery Paclitaxel IV Carboplatin IV BEV IV Bevacizumab every 3 wks until progression Every 21 days x 6 courses

14 …the Future is Now

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16 Novel Agents - Reolysin Reovirus Serotype 3 – –naturally occurring human reovirus In nature, reovirus infection is mild Reovirus –replicate specifically in and are cytopathic to cells possessing an activated Ras signaling pathway (Cancer cells) Reovirus Serotype 3 –Dearing Strain has been demonstrated to be effective against solid tumors when administered IV and IP OSU was the first institution in the world to have treated patients with ovarian cancer –Phase I completed

17 http://www.oncolyticsbiotech.com/reolysin

18 GOG 186 H Phase II TRINOVA 3 AMGEN PROTOCOL Recurrent Ovarian Cancer RANDOMIZERANDOMIZE Weekly taxol + Reolysin daily x 5 Weekly taxol

19 Not yet ready for humans… but close Safe, Targeted Antitumor Therapeutics (STAT3 Inhibitors) for Ovarian Cancer NOH moiety (HO-3867 and HO-4200 would function act as an anti- oxidant and it Selectively Target the Cancer cells HO-3867 compound mixed with the animal feed at 3 different levels (25, 50 & 100 ppm).

20 Efficacy of HO-3867 in vivo Untreated 25 ppm 50 ppm 100 ppm HO-3867 compound mixed with the animal feed at 3 different levels (25, 50 & 100 ppm).

21 STAT3 in Ovarian Cancer The active form of STAT3 (pSTAT3) has been identified in 60 percent of cancer cells including ovarian cancer. Clin.Cancer Res -2007 STAT3 has attracted much attention as a pharmacologic target HO-3867 Target STAT3, resulting inhibition of cell proliferation and induction of apoptosis In Silico Molecular Modeling pSTAT3 Tyr705 STAT3 pSTAT3 Ser727

22 The antioxidant-conjugated HO-3867 appears to be a safe and effective anticancer agent for ovarian cancer. HO-3867 might target, at least in part, STAT3 activation in the ovarian tumor

23 Survivorship Quality of Life Lance Armstrong Foundation (LAF) Multi-Disciplinary

24 How do we improve? Research –Phase I, II, III trials –GOG/NCI –Consortium –Collaborations –Institutional –Advocacy Groups –Private Personalized Medicine Molecular Genetics Psychosocial Behavioral

25 Why do we do what we do? Why are we here?

26 Survivors!

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