Transcript Ovarian Cancer Update - Kentucky Cancer Registry

OVARIAN
CANCER
UPDATE
KENTUCKY CANCER
REGISTRY
9/8/2016
Erica Takimoto, D.O.,
F.A.C.O.O.G.
Gynecologic Oncology
My Aunt Kris
Diagnosed 9/2013
OVARIAN CANCER IN
2016
-22,800 estimated new cases
-1.3% of all cancer cases
- 14,240 deaths
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
OVARIAN CANCER IN
2016
-Localized (15%)
Confined to Primary Site
-Regional (19%)
Spread to Regional
Lymph Nodes
-Distant (60%)
Cancer Has Metastasized
-Unknown (6%)Unstaged
OVARIAN CANCER IN
2016
Five year
survival of
46.2%
CT SCAN IMAGE
CT SCAN IMAGE
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”
INTRAOPERATIVE
FINDINGS OF
OVARIAN CANCER
INTRAOPERATIVE
FINDINGS OF
OVARIAN CANCER
INTRAOPERATIVE
FINDINGS OF
OVARIAN CANCER
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
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
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%
PRIMARY
THERAPY
SWOG
-TAXOL 175MG/M2 Q28D
-3 VS 12 CYCLES
MAINTENANCE
-PFS IMPROVED FOR 12C
-28 VS 21 MOS
RECURRENCE
-THE PROBLEM OF RECURRENCE
-WITHIN FIRST 6 MOS – RESISTANT
-GREATER THAN 6 MOS – SENSITIVE
-TYPICAL SCENARIO
-10-12 mos relapse
-5-6 mos relapse
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
CHEMO IN THE
RECURRENT
SETTING
CHEMO IN THE
PLATINUM
SENSITIVE
RECURRENT
SETTING
-STANDARD RECURRENT REGIMEN:
-CARBOPLATIN / PACLITAXEL
-CARBOPLATIN AUC 4 /GEMCITABINE 1000MG DAY
1,8
-CARBOPLATIN / PLD Q 28D
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
CHEMO IN THE
PLATINUM
RESISTANT
RECURRENT
SETTING
-WEEKLY TAXOL 80MG/M2
-PLD 50MG/M2 Q 28D
-TOPOTECAN 1-2MG/M2 X5D, X3D, WEEKLY Q21D
ALTERNATE
CHEMO
AGENTS
• HOW TO CHOOSE AGENT
ALTERNATE
CHEMO
AGENTS
• 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
• BEVACIZUMAB
ALTERNATE
CHEMO
AGENTS
-HUMANIZED MONOCLONAL Ab
-VEGF INHIBITION
-ANTIANGIOGENIC
ALTERNATE
CHEMO
AGENTS
• BEVACIZUMAB
-PRIMARY SETTING:
-GOG 218, ICON-7
-MAINTENANCE:
-AGO-OVAR 16
-RECURRENCE:
-GOG170D – RR 16-21%
-GOG 213 – PLATINUM SENSITIVE
• BEVACIZUMAB
ALTERNATE
CHEMO
AGENTS
-GRADE 2+ HTN -> PRES
-ACE (lisinopril 10qd) or CCB
-GI PERFORATION / FISTULA – 11%
ALTERNATE
CHEMO
AGENTS
• Poly-ADP-Ribose
Polymerase (PARP)
INHIBITORS-OLAPARIB
-ENZYME WITH CRITICAL ROLE IN
SSDNA BREAKS – BASE EXCISION
REPAIR
-ACCUMULATION OF SS BREAKS ->
DOUBLE STRANDED BREAKS->
SYNTHETIC LETHALITY
ALTERNATE
CHEMO
AGENTS
• Poly-ADP-Ribose
Polymerase (PARP)
INHIBITORS-OLAPARIB
ALTERNATE
CHEMO
AGENTS
• Poly-ADP-Ribose
Polymerase (PARP)
INHIBITORS-OLAPARIB
-HOMOLOGOUS RECOMBINATION
DEFICIENCY – 50% HGS
-BRCA 1/2 GERMLINE MUTATION
15-20%
-SOMATIC MUTATIONS
ALTERNATE
CHEMO
AGENTS
• Poly-ADP-Ribose Polymerase
(PARP) INHIBITORSOLAPARIB
-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
CLINICAL
TRIALS
• AVAILABLE AT NORTON
CLINICAL
TRIALS
-GOG 0225 – OBSERATIONAL
STUDY DIET AND PHYSICAL
ACTIVITY POST TREATMENT
-GYN 14-18
-ADVANCED RELAPSED EOC
-TRABECTEDIN/DOXIL
-GYN 15-01 – LOW CA125,
PLATINUM SENSITIVE
-GOG 3005
• NRG/GOG TRIALS
-NRG GY001 - CABOZANTINIB
CLINICAL
TRIALS
-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)
-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
STILL
GARDENING
AWAY