Presentation on theme: "“Taking Care of Tomorrows Patient Better than Today”… the Future is Now Set A1 – Title Slide David O’Malley, M.D."— Presentation transcript:
1“Taking Care of Tomorrows Patient Better than Today”… the Future is Now Set A1 – Title SlideDavid O’Malley, M.D.
2Describe the Collaborative Trials (GOG) PastPresentFutureDiscuss Ovarian Cancer Research at The James Cancer Center – OSUSet A1 – Content Slide
3Have we made improvements? Are we doing any good? Set A1 – Content SlideSalani, et al. Overview of epithelial ovarian cancer and updates in management strategies, Expert Rev. Obstet. Gynecol. (2009)
4Talking the same language Ovarian Carcinoma -Talking the same languageStagingPrimary cytoreductionIntervalCytoreductionSecondaryDiagnosisProgressionDeathSymptomsChemotherapy #1Chemo #2Chemo #3+ConsolidationSet A1 – Content SlideCureSupportiveCare
5Gynecologic Oncology Group (GOG) Adjuvant/First Line TherapyGOG 218 (NEJM just published)GOG 252 (just completed enrollment)GOG 262 (just completed enrollment)Recurrent TherapyGOG 213 (just completed enrollment, except for surgery questionSet A1 – Content Slide
6Bevacizumab every 3 wks for 16 cycles GOG 218 Study Scheme Bevacizumab during Treatment and as MaintenanceMaintenancen = 1873Control arm:Carboplatin AUC 6 d1Paclitaxel 175 mg/m2 d1Placebo d1RANDOMIZEPlacebo x 16 cyclesPreviously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancerStage III optimal (macroscopic)Stage III suboptimalStage IVExperimental arm:Carboplatin AUC 6 IV d 1Paclitaxel 175 mg/m2 IV d 1Bevacizumab 15 mg/kg d1Set A1 – Content SlideExperimental arm:Carboplatin AUC 6 IV d 1Paclitaxel 175 mg/m2 IV d 1Bevacizumab 15 mg/kg d1Bevacizumab every 3 wks for 16 cyclesEvery 21 days x 6 coursesBurger RA, NEJM 2012
7218 Progression Free Survival Arm ICP + PLA → PLA (n=625)Arm IICP + BEV → PLA (n=625)Arm IIICP + BEV → BEV (n=623)Patients with event, n (%)375(60)405(67)363(71)Median PFS, months10.411.513.9HR (stratified) (95% CI)0.864(0.759–0.996)0.726(0.627–0.840)One-sided log-rank p-value0.0218*<0.0001a1.00.90.80.220.127.116.11.30.20.1Median follow-up: 17.4 monthsProportion surviving progression freeMedianII vs IIII vs IMonths since randomizationBurger RA, J Clin Oncol 2010;28(18S):
8GOG Statistical Manual IV versus IP (different regimens) Bevacizumab during Treatment and as MaintenanceMaintenancePaclitaxel 80 mg/m2 IV days 1, 8, 15Carboplatin AUC 6 IV day 1Bevacizumab 15 mg/kg IV on day 1 beginning on cycle 2RANDOMIZEPreviously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancerStage II. III optimalStage III suboptimal (some)Stage IV (some)Paclitaxel 80 mg/m2 IV days 1, 8, 15Carboplatin AUC 6 IP day 1Bevacizumab 15 mg/kg IV on day 1 beginning on cycle 2Bevacizumab x 16 cyclesSet A1 – Content SlidePaclitaxel 135 mg/m2 IV on day 1Cisplatin 75 mg/m2 IP on day 2Paclitaxel 60 mg/m2 IP on day 8Bevacizumab 15 mg/kg IV on day 1 beginning on cycle 2GOG Statistical Manual
9OPTIONAL Bevacizumab until PROGRESSION GOG Statistical Manual Different taxol IV schedules *OPTIONAL Bevacizumab during Treatment and as MaintenanceMaintenance*Paclitaxel 80 mg/m2 IV days 1, 8,15Carboplatin AUC 6 IV day 1*Bevacizumab 15 mg/kg IV on day 1RANDOMIZEPreviously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancerStage II. III optimal suboptimalStage IVOPTIONAL Bevacizumab until PROGRESSIONSet A1 – Content SlidePaclitaxel 175 mg/m2 IV days 1Carboplatin AUC 6 IV day 1*Bevacizumab 15 mg/kg IV on day 1GOG Statistical Manual
10Anti VEGF and angiopoietin agent TRINOVA - 3(AMG 386)Anti VEGF and angiopoietin agentMaintenancen = 2000Control arm:Carboplatin AUC 5-6 d1Paclitaxel 175 mg/m2 d1Placebo weeklyRANDOMIZEWeekly Placebox 18 monthsPreviously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancerPost operative Stage III, IVNeoadjuvant2:1 randomizationSet A1 – Content SlideExperimental arm:Carboplatin AUC 5-6 IV d 1Paclitaxel 175 mg/m2 IV d 1AMG 386 weeklyAMG 386 x 18 monthsTRINOVA 3 AMGEN PROTOCOL
11GOG Statistical Manual NEXT STEP in GOGPARP inhibitorsMaintenancePaclitaxelCarboplatinPLACEBORANDOMIZEPLACEBOPaclitaxelCarboplatinPARPPreviously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancerStage II. III optimalStage III suboptimalStage IVNEOADJUVANT?PaclitaxelCarboplatinPLACEBOSet A1 – Content SlidePARPPaclitaxelCarboplatinPARPGOG Statistical Manual
13Bevacizumab every 3 wks until progression GOG Statistical Manual Bev with treatment UNTIL PROGRESSIONPlus Surgery questionSurgical candidate?RANDOMIZERANDOMIZEPaclitaxel IVCarboplatin IVSurgeryRecurrent Ovarian Cancer in patients with a treatment free interval for at least 6 months from primary therapyYesNo SurgeryMaintenancePaclitaxel IVCarboplatin IVBEV IVBevacizumab every 3 wks until progressionSet A1 – Content SlideNoEvery 21 days x 6 coursesGOG Statistical Manual
16Novel Agents - Reolysin Reovirus Serotype 3 –naturally occurring human reovirusIn nature, reovirus infection is mildReovirusreplicate specifically in and are cytopathic to cells possessing an activated Ras signaling pathway (Cancer cells)Reovirus Serotype 3Dearing Strain has been demonstrated to be effective against solid tumors when administered IV and IPOSU was the first institution in the world to have treated patients with ovarian cancerPhase I completedSet A1 – Content Slide
19Not yet ready for humans… but close Safe, Targeted Antitumor Therapeutics (STAT3 Inhibitors) for Ovarian CancerNOH moiety (HO-3867 and HO-4200 would function act as an anti-oxidant and it Selectively Target the Cancer cellsHO-3867 compound mixed with the animal feed at 3 different levels (25, 50 & 100 ppm).Set A1 – Content Slide
20Efficacy of HO-3867 in vivoUntreated25 ppm50 ppm100 ppmDays2004006008001000120014710131720253035Tumor Growth (mm3)Tumor – N=625PPM – N=850PPM – N=8100PPM –N=8HO-3867 compound mixed with the animal feed at 3 different levels (25, 50 & 100 ppm).
21STAT3 in Ovarian CancerThe active form of STAT3 (pSTAT3) has been identified in 60 percent of cancer cells including ovarian cancer.Clin.Cancer Res -2007STAT3 has attracted much attention as a pharmacologic targetHO-3867 Target STAT3, resulting inhibition of cell proliferation and induction of apoptosisIn Silico Molecular ModelingpSTAT3Tyr705STAT3Ser727
22The 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 tumorSet A1 – Content Slide
23Survivorship Quality of Life Lance Armstrong Foundation (LAF) Multi-DisciplinarySet A1 – Content Slide
24How do we improve? Research Personalized Medicine Behavioral Phase I, II, III trialsGOG/NCIConsortiumCollaborationsInstitutionalAdvocacy GroupsPrivatePersonalized MedicineMolecularGeneticsPsychosocialBehavioralSet A1 – Content Slide
25Why do we do what we do?Set A1 – Content SlideWhy are we here?