Uptodate do Tratamento de 1 linha do Câncer de Ovário Brasília 2012 Fernando Fernando Cotait Maluf Cotait Maluf Diretor do Serviço de Oncologia Clínica Diretor do Serviço de Oncologia Clínica Beneficência Portuguesa Beneficência Portuguesa Médico Integrante da Clínica Oncovida Médico Integrante da Clínica Oncovida ([email protected]) ([email protected])
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Uptodate do Tratamento de 1 0 linha do Câncer de Ovário Brasília 2012 Fernando Cotait Maluf Diretor do Serviço de Oncologia Clínica Beneficência Portuguesa.
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Uptodate do Tratamento de 10 linha do Câncer de Ovário
Brasília 2012
FernandoFernando Cotait Maluf Cotait MalufDiretor do Serviço de Oncologia ClínicaDiretor do Serviço de Oncologia Clínica
Beneficência PortuguesaBeneficência Portuguesa
Médico Integrante da Clínica OncovidaMédico Integrante da Clínica Oncovida
Carboplatin AUC 5 EV + Doxo Lipossomal 30 mg/m2 IV 1 h
cada 21 d x 6 ciclos
MITO-2
Sobrevida Livre de Progressão
Sobrevida Global
Análise de Subgrupo (SG)
Toxicidade
Carboplatina/doxorrubicina lipossomal: menos alopecia e neuropatia
Carboplatina/paclitaxel: menos mielosupressão
Phase III Trial of Bevacizumab in the Primary Treatment of Advanced Epithelial Ovarian,
Primary Peritoneal, or Fallopian Tube Cancer: A Gynecologic Oncology Group (GOG) Study
R.A. Burger,1 M.F. Brady,2 M.A. Bookman,3
J.L. Walker,4 H.D. Homesley,5 J. Fowler,6 B.J. Monk,7 B.E. Greer,8 M. Boente,9 S.X. Liang10
1Fox Chase Cancer Center, Philadelphia, PA; 2Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY; 3University of Arizona Cancer Center, Tucson, AZ; 4University of Oklahoma Health Sciences Center,
Oklahoma City, OK; 5Brody School of Medicine, Greenville, NC; 6James Cancer Hospital at the Ohio State University, Hilliard, OH; 7University of California, Irvine
Medical Center, Orange, CA; 8Seattle Cancer Care Alliance, Seattle, WA; 9Minnesota Oncology and Hematology, Minneapolis, MN; 10State University of New York at Stony
Brook, Stony Brook, NY, USA
GOG-0218: Schema
Stratification variables:• PS• Stage/debulking status BEV 15 mg/kg
15 months
Paclitaxel (P) 175 mg/m2
Carboplatin (C) AUC 6
Carboplatin (C) AUC 6
Paclitaxel (P) 175 mg/m2
Carboplatin (C) AUC 6
Paclitaxel (P) 175 mg/m2
Placebo
PlaceboBEV 15 mg/kg
Front-line: Epithelial OV, PP or FT cancer
• Stage III optimal (macroscopic)
• Stage III suboptimal• Stage IV
n=1800 (planned)
I
II
III
Arm
1:1:1
GOG-0218: Analysis Plan
• Primary analysis
– Compare investigator-determined progression-free survival (PFS) for each BEV arm (CP + BEV; CP + BEV BEV) vs control (CP)
• If both results positive, compare CP + BEV BEV vs CP + BEV
– Disease progression based on: RECIST, global clinical deterioration, or CA-1251
Risk factor Total no. of patients Hazard ratio for Avastin (95% CI)
GOG performance status score
0 Arm II vs Arm I Arm III vs Arm I
626616
0.8770.710
1 or 2 Arm II vs Arm I Arm III vs Arm I
624632
0.9610.690
Age
<60 years Arm II vs Arm I Arm III vs Arm I
616630
0.9760.680
60–69 years Arm II vs Arm I Arm III vs Arm I
414408
0.8920.763
≥70 years Arm II vs Arm I Arm III vs Arm I
220210
0.8410.678
0.33 0.50 0.67 1.00 1.50 2.00 3.00
bevacizumab better Control better
GOG-0218: Overall Survival (OS)
• Events observed in 24% of patients at time of data lock• After primary endpoint changed from OS to PFS
– Unblinding to treatment assignment allowed at time of disease progression
OutcomeArm I
CP(n=625)
Arm IICP + BEV(n=625)
Arm IIICP + BEV BEV
(n=623)
Deaths, n (%)156
(25.0)150
(24.0)138
(22.2)
1-year survival, % 90.6 90.4 91.3
GOG-0218: Overall Survival Analysis At time of final PFS analysis (January 2010)
Arm ICP
(n=625)
Arm IICP + BEV(n=625)
Arm IIICP + BEV BEV
(n=623)
Patients with events, n (%)
156 (25.0)
150 (24.0)
138 (22.2)
Median, months 39.3 38.7 39.7
HRa
(95% CI)1.036
(0.827–1.297)0.915
(0.727–1.152)
One-sided p-value 0.361 0.252
Pro
po
rtio
n a
live
Months since randomization
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
00 12 24 36 48
aStratified analysis
625/625/623 442/432/437 173/162/171 46/39/40No. at risk
ICON7: A phase III Gynaecologic Cancer InterGroup (GCIG) trial of adding bevacizumab to standard
chemotherapy in women with newly diagnosed epithelial ovarian, primary
peritoneal or fallopian tube cancerTim Perren, Ann Marie Swart, Jacobus Pfisterer,
Jonathan Ledermann, Alain Lortholary, Gunnar Kristensen, Mark Carey, Philip Beale, Andreas Cervantes, Amit Oza
on behalf of GCIG ICON7 collaborators (MRC/NCRI, AGO-OVAR, GINECO, NSGO, ANZGOG, GEICO, NCIC-CTG)
Patient population
• Histologically confirmed epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer
• Prior surgical debulking with the aim of maximal surgical cytoreduction undertaken AND no planned further surgical debulking before disease progression
• FIGO stage• I–IIA if high risk: Grade 3 or clear cell histology (10%)
• IIB–IV: All grades and histological subtypes
• Patients with inoperable stage III/IV disease eligible after biopsy only if no further surgery planned
• ECOG performance status 0–2
28
Year 1 Years 2–3 Years 4–5
CT Baseline; after cycles 3 & 6; at 9 & 12 months Every 6 months As indicated
CA-125/clinical assessment
Every chemotherapy cycle; every 6 weeks during maintenance phase
Every 3 months Every 6 months
Stratification variables:• Stage & extent of debulking: I–
III debulked ≤1cm vs stage I–III debulked >1 cm vs stage IV and inoperable stage III
• Timing of intended treatment start≤4 vs >4 weeks after surgery
• GCIG group
Schema
Academic-led, industry-supported trial to investigate use of bevacizumab and to support licensing
Paclitaxel 175 mg/m2
Carboplatin AUC6
Carboplatin AUC6
Paclitaxel 175 mg/m2
18 cycles
R
n=1528*
Bevacizumab 7.5 mg/kg q3w
29
1:1
*Dec 2006 to Feb 2009*Dec 2006 to Feb 2009
Study endpoints
• Primary endpoint: Progression-free survival (PFS)• Disease progression defined by RECIST guidelines on
radiological, clinical or symptomatic progression
• CA-125 elevation alone not defined as disease progression
• 1520 patients randomised over 2 years (684 events) → 5% significance level, 90% power to detect: