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
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Gynecologic Cancer ASCO/ONS Highlights 2011 Association of Northern California Oncologists Lee-may Chen, MD Professor of Clinical Obstetrics, Gynecology,
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Gynecologic CancerASCO/ONS Highlights 2011
Association of Northern California Oncologists
Lee-may Chen, MDProfessor of Clinical Obstetrics, Gynecology, &
Reproductive SciencesDivision 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
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, 4/05-10/07Median 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 2010Abstract No: 5052
OCEANS: A randomized, double-blinded, placebo-controlled 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, H Parmar, LR Nycum, MA Sovak
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
BevacizumabA humanized anti-VEGF monoclonal antibodySingle-agent activity in recurrent ovarian cancer
21% response rate in 2nd/3rd line treatment
Carboplatin & Gemcitabine Improved response rate and PFS over single agent
Carboplatin47% vs 31% ORR, p=0.00168.6 vs 5.8mo PFS, HR 0.72 (p=0.0031)
Burger et al, J Clin Oncol 2007Pfisterer et al, J Clin Oncol, 2006
2 GI perforations 69d after bevacizumab23% 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 platinum-sensitive recurrent ovarian carcinoma.
ORR: 78.5% vs 57.4%, p< 0.0001PFS: 12.4mo vs 8.4mo, HR 0.48, p< 0.0001OS: 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, 12/06-2/09PFS: 19.0mo vs 17.3mo, HR 0.81, p=0.0041
Median follow-up: 28 mo. Overall HR 0.84, p=0.099Suboptimal 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 Shapira-Frommer, 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 2010Gelmon et al, ASCO 2010
Olaparib Maintenance
Platinum sensitive recurrent ovarian carcinoma with stable complete/partial response
2 or more prior platinum-containing regimensStratified by time to progression and response in last
platinum regimen, Jewish descentBRCA testing not required
Olaparib: 400mg PO BID vs Placebo
Evaluation for progression by RECIST criteriaPrimary objective: PFS
Abstract No: 5003
Olaparib Maintenance: Results
n=26516 countriesMedian PFS: 8.4mo vs 4.8mo, HR 0.35, p <
0.00001Median TTP: 8.3mo vs 3.7mo
50% olaparib, 16% placebo patients remain on treatment
9 patients on olaparib had > gr3 fatigue & 7 patients had > gr3 anemia4 patients on placebo had > gr3 fatigue & 4 patients had > gr3 abdominal painThe 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 platinum-sensitive recurrent ovarian carcinoma.
PFS: 8.4mo vs 4.8mo, HR 0.35, p< 0.00001TTP: 8.3mo vs 3.7mo, HR 0.35, p<0.00001OS: 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: 5004Abstract 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
Abstract No: 5001
88% White27% Prior hysterectomy54% Prior oral contraceptive pill use63% Prior hormone therapy9% Nulliparous4% Prior breast cancer17% Family history of breast or ovarian cancer