Gynecologic Cancer
ASCO/ONS Highlights 2011
Association of Northern California Oncologists
Lee-may Chen, MD
Professor of Clinical Obstetrics, Gynecology, &
Reproductive Sciences
Division of Gynecologic Oncology
UCSF Helen Diller Family Comprehensive Cancer Center
Objectives
Review, summarize, and interpret
new advances
and implement changes
in the treatment of gynecologic
malignancies presented at the 2011 ASCO
Annual Meeting
New Advances in Gyn Malignancies
Biological targets
Angiogenesis: Bevacizumab, Cabozantinib,
Sorafenib, Aflibercept, Temsirolimus
DNA damage repair: Olaparib, Iniparib
Folate receptor: Farletuzemab
Trabecditin
Pegylated liposomal doxorubicin and carboplatin (C-PLD)
versus paclitaxel and carboplatin (C-P) in platinum-sensitive
ovarian cancer (OC) patients (pts): Treatment at recurrence
and overall survival (OS) final analysis from CALYPSO
phase III GCIG trial
Phase III trial comparing pegylated liposomal doxorubicin & carboplatin
with paclitaxel & carboplatin,
n=976, 4/05-10/07
Median PFS: 11.3mo vs 9.4mo, HR 0.82, p=0.005
Most patients received subsequent treatment, but there was an imbalance
of crossover: C-PLD P, 34%, C-P PLD, 57%
Median follow-up: 40mo.
Median OS: 30.7mo vs 33.0mo, HR 0.99, p=0.87
Conclusion: Crossover treatment rate was higher in
C-P, OS was similar
Pujade-Lauraine et al, J Clin Oncol 2010
Abstract No: 5052
OCEANS: A randomized, double-blinded, placebocontrolled phase III trial of chemotherapy with or without
bevacizumab (BEV) in patients with platinum-sensitive
recurrent epithelial ovarian (EOC), primary peritoneal
(PPC), or fallopian tube cancer (FTC).
C Aghajanian, NJ Finkler, T Rutherford, DA Smith, J Yi,
Parmar, LR Nycum, MA Sovak
H
Memorial Sloan-Kettering Cancer Center, New York, NY;
Florida Hospital Gynecologic Oncology, Florida Hospital
Cancer Institute, Orlando, FL; Yale University School of
Medicine, New Haven, CT; Northwest Cancer Specialists,
Vancouver, WA; Genentech Inc., South San Francisco, CA;
Forsyth Regional Cancer Center, Winston-Salem, NC
Abstract No: LBA5007
OCEANS: Rationale
Bevacizumab
A humanized anti-VEGF monoclonal antibody
Single-agent activity in recurrent ovarian cancer
21% response rate in 2nd/3rd line treatment
Carboplatin & Gemcitabine
Improved response rate and PFS over single agent
Carboplatin
47% vs 31% ORR, p=0.0016
8.6 vs 5.8mo PFS, HR 0.72 (p=0.0031)
Burger et al, J Clin Oncol 2007
Pfisterer et al, J Clin Oncol, 2006
Abstract No: LBA5007
OCEANS: Treatment exposure
Median # cycles
CG+Pl
(n=233)
CG+Bev
(n=247)
Chemotherapy
6
(1-10)
6
(1-10)
Bevacizumab/Placebo
10
(1-36)
12
(1-43)
Abstract No: LBA5007
Abstract No: LBA5007
OCEANS: Toxicities
AEs of special interest
CG+Pl
n=233
CG +Bev
n=247
Neutropenia, > gr3
56
58
Febrile neutropenia
2
2
Hypertension, > gr3
<1
17
Fistula/abscess
<1
2
GI perforation
0
0
Proteinuria
1
9
2 GI perforations 69d after bevacizumab
23% of discontinuation in CG + Bev were due to HTN,
proteinuria
Abstract No: LBA5007
OCEANS: Conclusions
Carboplatin, gemcitabine, & bevacizumab, followed by
bevacizumab until progression provides a clinically
meaningful benefit over chemotherapy alone in platinumsensitive recurrent ovarian carcinoma.
ORR: 78.5% vs 57.4%, p< 0.0001
PFS: 12.4mo vs 8.4mo, HR 0.48, p< 0.0001
OS: 35.5mo vs 29.9mo, HR 0.75, p=0.094, not yet mature
Safety data
A new option for recurrent platinum-sensitive ovarian
carcinoma
Abstract No: LBA5007
Result of interim analysis of overall survival in the GCIG
ICON7 phase III randomized trial of bevacizumab in women
with newly diagnosed ovarian cancer
ICON7: High risk and advanced ovarian cancer treated with debulking
surgery, then: Taxol/Carboplatin x 6 cycles, followed by bevacizumab
through 18 cycles versus no further treatment
N=1528, 12/06-2/09
PFS: 19.0mo vs 17.3mo, HR 0.81, p=0.0041
Median follow-up: 28 mo.
Overall HR 0.84, p=0.099
Suboptimal Stage III + Stage IV
OS: 36.6mo vs 28.8mo, HR 0.64, p=0.0022
Conclusion: Overall trend for improvement by adding Bev
Abstract No: LBA5006
Phase II randomized placebo-controlled study of olaparib
(AZD2281) in patients with platinum-sensitive relapsed
serous ovarian cancer (PSR SOC)
JA Ledermann, P Harter, C Gourley, M Friedlander, IB
Vergote, GJS Rustin, C Scott, W Meier, R ShapiraFrommer, T Safra, D Matei, E Macpherson, C Watkins, J
Carmichael, U Matulonis
UCL Cancer Institute and UCL Hospitals, London, United Kingdom; Kliniken
Essen Mitte, Essen, Germany; Edinburgh Cancer Research UK Centre,
Edinburgh, United Kingdom; Department of Medical Oncology, Prince of
Wales Hospital and Prince of Wales Clinical School, UNSW, Sydney,
Australia; University Hospital Leuven, Leuven, Belgium; Mount Vernon
Cancer Centre, Middlesex, United Kingdom; The Walter and Eliza Hall
Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia;
Evangelical Hospital, Düsseldorf, Germany; Oncology Institute, Chaim Sheba
Medical Center, Ramat-Gan, Israel; Department of Oncology, Tel Aviv
Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University,
Tel Aviv, Israel; Indiana University Simon Cancer Center, Indianapolis, IN;
AstraZeneca, Macclesfield, United Kingdom; Dana-Farber Cancer Institute,
Boston, MA
Abstract No: 5003
PARP Inhibitors
Selectively potent in BRCA1/2 deficient tumors
33-41% RR in Phase II study in recurrent ovarian cancer
24% RR in BRCA1/2 intact ovarian cancer
Audeh et al, Lancet 2010
Gelmon et al, ASCO 2010
Olaparib Maintenance
Platinum sensitive recurrent ovarian carcinoma with stable
complete/partial response
2 or more prior platinum-containing regimens
Stratified by time to progression and response in last platinum
regimen, Jewish descent
BRCA testing not required
Olaparib: 400mg PO BID vs Placebo
Evaluation for progression by RECIST criteria
Primary objective: PFS
Abstract No: 5003
Olaparib Maintenance: Results
n=265
16 countries
Median PFS: 8.4mo vs 4.8mo, HR 0.35, p <
0.00001
Median TTP: 8.3mo vs 3.7mo
50% olaparib, 16% placebo patients remain
on treatment
Abstract No: 5003
Olaparib Maintenance: Toxicities
Adverse events
Nausea
Fatigue
Vomiting
Anemia
Placebo
n=129
Olaparib
n=136
35%
38%
14%
5%
68%
49%
32%
17%
9 patients on olaparib had > gr3 fatigue & 7 patients had > gr3 anemia
4 patients on placebo had > gr3 fatigue & 4 patients had > gr3 abdominal pain
The majority of AEs were grade 1 or 2
Abstract No: 5003
Olaparib Maintenance: Conclusions
Maintenance treatment with olaparib provided a significant
improvement in progression-free survival in platinumsensitive recurrent ovarian carcinoma.
PFS: 8.4mo vs 4.8mo, HR 0.35, p< 0.00001
TTP: 8.3mo vs 3.7mo, HR 0.35, p<0.00001
OS: not yet mature
Well tolerated
A new option for maintenance treatment in recurrent
platinum-sensitive ovarian carcinoma
Abstract No: 5003
Iniparib
A phase II trial of iniparib (BSI-201) in combination with
gemcitabine/carboplatin (GC) in patients with platinum-sensitive
recurrent ovarian cancer
n=41, 71% ORR, 9.4mo PFS
A phase II trial of iniparib (BSI-201) in combination with
gemcitabine/carboplatin (GC) in patients with platinum-resistant
recurrent ovarian cancer
n=48, 32% ORR, 5.9mo PFS
Conclusions: Activitity without unexpected toxicities
Abstract No: 5004
Abstract No: 5005
Effect of screening on ovarian cancer mortality in the
Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer
randomized screening trial
SS Buys, E Partridge, A Black, C Johnson, L Lamerato, C
Isaacs, D Reding, R Greenlee, B Kessel, M Fouad, D Chia,
L Ragard, J Rathmell, P Hartge, P Pinsky, G Izmirlian, J
Xu, P Prorok, CD Berg
Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT;
University of Alabama at Birmingham, Birmingham, AL; National
Cancer Institute, Bethesda, MD; Henry Ford Health System, Detroit,
MI; Henry Ford Hospital, Detroit, MI; Lombardi Comprehensive
Cancer Center, Washington, DC; Marshfield Clinic Research
Foundation, Marshfield, WI; Marshfield Medical Center, Marshfield,
WI; Pacific Health Research Education Institute, Honolulu, HI;
Minority Health and Health Disparities Research Center, Birmingham,
AL; Department of Pathology and Laboratory Medicine, Los Angeles,
CA; Westat, Inc., Rockville, MD; Information Management Services,
Inc., Bethesda, MD; Division of Cancer Prevention, NCI, Bethesda,
MD
Abstract No: 5001
PLCO: Background
11/93-7/01, n=78,216 women ages 55-74
10 centers nationally
Intervention: baseline, then annual CA125 (5 yrs)
and transvaginal ultrasound (3 yrs)
Abstract No: 5001
PLCO: Patient Characteristics
88% White
27% Prior hysterectomy
54% Prior oral contraceptive pill use
63% Prior hormone therapy
9% Nulliparous
4% Prior breast cancer
17% Family history of breast or ovarian
cancer
85% 73% compliance with screening
Abstract No: 5001
PLCO: Results
CA125: 1.4-1.8% positive screen
Transvaginal ultrasound: 2.9-4.6% positive screen
Ovarian cancers diagnosed
212 cases in screening arm
(5.7 per 10,000 person years), 77% Stage III/IV
176 in usual care arm
(4.7 per 10,000 person years), 78% Stage III/IV
RR 1.21, 95% CI 0.99-1.48
Abstract No: 5001
PLCO: Results
Ovarian cancer deaths
118 in screening arm (3.1 per 10,000 person years)
100 in usual care (2.6 per 10,000 person years)
RR 1.18, 95% CI 0.82-1.71
All cause mortality, RR 1.01, 95% CI 0.96-1.06
Abstract No: 5001
PLCO: Results
3285 false positive CA125/ultrasound tests
1080 (32.9%) underwent surgery
222 distinct major complications
20.6 complications per 100 surgical procedures
-Infection, Surgical, Cardiovascular or pulmonary
Oophorectomy procedures
1771 (7.7%) in screening arm
1304 (5.8%) in usual care arm
RR 1.33, 95% CI 1.24-1.43
Abstract No: 5001
PLCO: Conclusions
Annual CA125 and transvaginal ultrasound
screening does not reduce disease-specific
mortality in average risk postmenopausal
women.
Screening does increase invasive medical
procedures, with associated harms and
complications.
Abstract No: 5001
Ovarian Cancer Management
Screening
Suspicious Mass
Suspicious Symptoms
Hereditary Risks
Examination, Imaging, CA125
Laparotomy vs laparoscopy
Staging
Cytoreduction
Bx Neoadjuvant chemotherapy
IV Chemotherapy, possible dose dense
IV/IP Chemotherapy
Possible Interval debulking surgery
Clinical follow-up
Maintenance chemotherapy
Recurrence therapy
ASCO 2011: Gyn Takeaway
OCEANS: Consider bevacizumab in recurrent
ovarian cancer
PARP inhibitors: Consider olaparib for
maintenance in ovarian cancer
Screening: Annual CA125 & USN ineffective
for detecting ovarian cancer in low risk
women