1. Ovarian cancer update Kentucky cancer Registry 9/8/2016
Erica Takimoto, D.O., F.A.C.O.O.G.
Gynecologic Oncology

2. Symptoms & diagnosis Insidious onset Bloating
Increased abdominal girth
Pelvic mass on CT/US/MRI
No good screening test – CA 125, OVA1
Clinical acumen is paramount
Family history

3. Primary therapy -Surgical or Medical management as first line ?
-Previous thought was primary surgical cytoreduction or “debulking”
-Disease volume less than 1cm was considered “optimal”

4. Primary Therapy
-Recent change in definition of “optimal” to No Visible Residual Disease (NRD) or “R0”
-With previous definition of <1cm, approx 75% of pts
-With new goal of NRD, approx 25% of pts
-Initially suggested by German Study and validated by Rob Coleman et al

5. Primary Therapy
-New data suggests Neoadjuvant Chemotherapy (NAC) beneficial in certain conditions (EORTC, SEER, CHORUS)
-Key decision point in patients with new diagnosis
-Will impact OS
-NCCN / ASCO / SGO - all EOC pts need BRCA status
VUS treated as negative

6. PRIMARY THERAPY Frontline SOC -TAXANE / PLATINUM DOUBLET
-CARBOPLATIN AUC 6
-TAXOL 175MG/M2 OR WEEKLY DOSE DENSE 80MG/M2
-INTRAPERITONEAL
-GOG172
-PATHOLOGIC CR WITH NAC IS LOW – 5%

7. PRIMARY THERAPY MAINTENANCE SWOG -TAXOL 175MG/M2 Q28D -3 VS 12 CYCLES
-PFS IMPROVED FOR 12C
-28 VS 21 MOS
PRIMARY THERAPY
MAINTENANCE

8. CHEMO IN THE RECURRENT SETTING
-THE PROBLEM OF RECURRENCE
-WITHIN FIRST 6 MOS – RESISTANT
-GREATER THAN 6 MOS – SENSITIVE
-TYPICAL SCENARIO
mos relapse
-5-6 mos relapse

9. ROLE OF SECONDARY CYTOREDUCTION
CAVEATS
-PLATINUM RESISTANT
-CARCINOMATOSIS
IDEAL CANDIDATE
-LONG TREATMENT FREE INTERVAL **>18-30 MOS
-PREVIOUSLY RESPONSIVE TO CHEMOTHERAPY
-LIMITED SITES OF DISEASE
ROLE OF SECONDARY CYTOREDUCTION

10. CHEMO IN THE PLATINUM SENSITIVE RECURRENT SETTING
-STANDARD RECURRENT REGIMEN:
-CARBOPLATIN / PACLITAXEL
-CARBOPLATIN AUC 4 /GEMCITABINE 1000MG DAY 1,8
-CARBOPLATIN / PLD Q 28D

11. CHEMO IN THE PLATINUM SENSITIVE RECURRENT SETTING
-OCEANS TRIAL
-CARBO/GEM +/- BEV
-IMPROVED PFS WITH NO OS
-P=0.056, CLINICALLY MEANINGFUL WITH 5 MOS BENEFIT

12. CHEMO IN THE PLATINUM RESISTANT RECURRENT SETTING
-WEEKLY TAXOL 80MG/M2
-PLD 50MG/M2 Q 28D
-TOPOTECAN 1-2MG/M2 X5D, X3D, WEEKLY Q21D

13. ALTERNATE chemo agents HOW TO CHOOSE AGENT
ABLE TO PREDICT WHO WILL RESPOND
BRCA STATUS
NEXT GEN SEQUENCING
LOOKING FOR BIOMARKER LOSS OF HETEROZYGOSITY
40+ GENES INVOLVED IN HR DEFICIENCY (PTEN)
MULTIPLE LINES OF THERAPY
ALTERNATE chemo
agents

14. ALTERNATE chemo agents BEVACIZUMAB -HUMANIZED MONOCLONAL Ab
-VEGF INHIBITION
-ANTIANGIOGENIC
-PRIMARY SETTING:
-GOG 218, ICON-7
-MAINTENANCE:
-AGO-OVAR 16
-RECURRENCE:
-GOG170D – RR 16-21%
-GOG 213 – PLATINUM SENSITIVE
-GRADE 2+ HTN -> PRES
-ACE (lisinopril 10qd) or CCB
-GI PERFORATION / FISTULA – 11%
ALTERNATE chemo
agents

15. ALTERNATE chemo agents
Poly-ADP-Ribose Polymerase (PARP) INHIBITORS-OLAPARIB
-ENZYME WITH CRITICAL ROLE IN SSDNA BREAKS – BASE EXCISION REPAIR
-HOMOLOGOUS RECOMBINATION DEFICIENCY – 50% HGS
-BRCA 1/2 GERMLINE MUTATION %
-SOMATIC MUTATIONS
-ACCUMULATION OF SS BREAKS -> DOUBLE STRANDED BREAKS-> SYNTHETIC LETHALITY
ALTERNATE chemo
agents

16. ALTERNATE chemo agents
Poly-ADP-Ribose Polymerase (PARP) INHIBITORS- OLAPARIB
-PRIMARY SETTING: *GOG3005
-MAINTENANCE:
-SOLO 1,2
-OLAPARIB 400MG BID
-RECURRENCE:
-ARIEL 2 RUCAPARIB 600BID
-OLAPARIB 4TH LINE AGENT MONOTHERAPY IN PTS WITH BRCA/ HRD
-GI DISTURBANCE
-HRD NEXT GEN SEQUENCING
ALTERNATE chemo
agents

17. CLINICAL TRIALS AVAILABLE AT NORTON
-GOG 0225 – OBSERATIONAL STUDY DIET AND PHYSICAL ACTIVITY POST TREATMENT
-GYN 14-18
-ADVANCED RELAPSED EOC
-TRABECTEDIN/DOXIL
-GYN – LOW CA125, PLATINUM SENSITIVE
-GOG 3005
CLINICAL TRIALS

18. CLINICAL TRIALS NRG/GOG TRIALS -NRG GY003 – NIVOLUMIMAB +/- IPILUMIMAB
-NRG GY001 - CABOZANTINIB
-NRG GY003 – NIVOLUMIMAB +/- IPILUMIMAB
-NRG GY004 – OLAPARIB PLATINUM SENSITIVE OV CA
-NRG GY005 – CEDIRANIB PLATINUM RESISTANT OV CA
-NRG GY007 – NEOADJUVANT RUXOLITINIB (JAK 1/2 INHIBITOR)
CLINICAL TRIALS
-GOG 3008 – CERULEAN CRLX101 + WEEKLY CISPLATIN IN RECURRENCE
-GOG3011 – IMMUNOGEN MIVETUXIMAB SORAVTANSINE VS INVESTIGATOR CHOICE IN FR-ALPHA POSITIVE RECURRENT OV CA
-GOG3012 – TESARO NIRAPARIB MAINTENANCE IN HRD POSITIVE OV CA