gynecologic cancer asco/ons highlights 2011 association of northern california oncologists lee-may...
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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
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, 4/05-10/07Median 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
Abstract No: LBA5007
OCEANS: Treatment exposure
Median # cycles CG+Pl CG+Bev
(n=233) (n=247)
Chemotherapy 6 6
(1-10) (1-10)
Bevacizumab/Placebo 10 12
(1-36) (1-43)Abstract No: LBA5007
Abstract No: LBA5007
OCEANS: Toxicities
AEs of special interest CG+Pl CG +Bevn=233 n=247
Neutropenia, > gr3 56 58Febrile neutropenia 2 2Hypertension, > gr3 <1 17Fistula/abscess <1 2GI perforation 0 0Proteinuria 1 9
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
Abstract No: 5003
Olaparib Maintenance: Toxicities
Adverse events Placebo Olaparibn=129 n=136
Nausea 35% 68%Fatigue 38% 49%Vomiting 14% 32%Anemia 5% 17%
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
85% 73% compliance with screening
PLCO: Results
CA125: 1.4-1.8% positive screenTransvaginal ultrasound: 2.9-4.6% positive screen
Ovarian cancers diagnosed212 cases in screening arm
(5.7 per 10,000 person years), 77% Stage III/IV176 in usual care arm
(4.7 per 10,000 person years), 78% Stage III/IVRR 1.21, 95% CI 0.99-1.48
Abstract No: 5001
PLCO: Results
Ovarian cancer deaths118 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 tests1080 (32.9%) underwent surgery222 distinct major complications 20.6 complications per 100 surgical procedures
-Infection, Surgical, Cardiovascular or pulmonary
Oophorectomy procedures1771 (7.7%) in screening arm1304 (5.8%) in usual care armRR 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
Suspicious MassSuspicious SymptomsHereditary Risks
Examination, Imaging, CA125 Laparotomy vs laparoscopy
StagingCytoreductionBx Neoadjuvant chemotherapy
IV Chemotherapy, possible dose denseIV/IP ChemotherapyPossible Interval debulking surgery
Clinical follow-upMaintenance chemotherapy
Screening
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