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
Uptodate do Tratamento de 10 linha do Câncer de Ovário
Enfoque:
- esquemas de 10 linha
- MITO-2: CD vs CP
-esquemas de 10 linha com BEV
- GOG 218 e ICON 7: CP-BEV vs CP
Piganta E et al, J Clin Oncol, Piganta E et al, J Clin Oncol, 20112011
Critério Inclusão:Critério Inclusão:
• Câncer de ovário Câncer de ovário epitelialepitelial
• Estádio Ic-IVEstádio Ic-IV• < 76 anos< 76 anos• ECOG 0-2ECOG 0-2
RANDOMIZAÇÃO
Carboplatina AUC 5 EV + Paclitaxel 175 mg/m2 IV 3
cada 21 d x 6 ciclos
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
– Planned sample size of 1800 based on:
• 90% power to detect PFS hazard ratio (HR) 0.77
– Median PFS shift: 14.0 months 18.2 months
• Secondary analyses: Overall survival (OS), safety, quality of life; correlative laboratory studies
1. Gynecologic Cancer Intergroup Criteria - Rustin et al. J Natl Cancer Inst 2004
GOG-0218: Key Eligibility Criteria
• Histologic diagnosis of epithelial OV, PP, or FT cancer
• Following maximal debulking surgery: stage III optimal (macroscopic residual disease 1 cm) or suboptimal (>1 cm), or stage IV
• No prior chemotherapy
• 1–12 weeks after initial surgery
• GOG PS 0–2
• No history of significant vascular events
• No evidence of intestinal obstruction requiring parenteral support
• Written informed consent
GOG-0218: Baseline Clinical Characteristics
Characteristic
Arm ICP
(n=625)
Arm IICP + BEV
(n=625)
Arm IIICP + BEV BEV
(n=623)
Median age, years (range) 60 (25–86) 60 (24–88) 60 (22–89)
Race, n (%)
Non-Hispanic white 526 (84) 519 (83) 521 (84)
Asian 41 (7) 37 (6) 39 (6)
Non-Hispanic black 25 (4) 28 (5) 27 (4)
Hispanic 21 (3) 28 (5) 25 (4)
Other, specified 8 (1) 5 (<1) 4 (<1)
GOG PS, n (%)
0 311 (50) 315 (50) 305 (49)
1 272 (44) 270 (43) 267 (43)
2 42 (7) 40 (6) 51 (8)
Percentages may not total 100% due to rounding or categorization
GOG-0218: Baseline Surgical–PathologicCharacteristics
Characteristic, n (%)
Arm ICP
(n=625)
Arm IICP + BEV(n=625)
Arm IIICP + BEV BEV
(n=623)
Stage/residual size
III optimal (macroscopic) 218 (35) 205 (33) 216 (35)
III suboptimal 254 (41) 256 (41) 242 (39)
IV 153 (25) 164 (26) 165 (27)
Histology
Serous 543 (87) 523 (84) 525 (84)
Endometrioid 20 (3) 15 (2) 25 (4)
Clear cell 11 (2) 23 (4) 18 (3)
Mucinous 8 (1) 5 (<1) 8 (1)
Tumor grade
3a 412 (66) 435 (70) 430 (69)
2 94 (15) 77 (12) 92 (15)
1 33 (5) 28 (4) 16 (3)
Not specified/pending 86 (14) 85 (14) 85 (14)
Percentages may not total 100% due to rounding or categorizationaGrade 3 includes all clear cell tumors
GOG-0218: Baseline Surgical–PathologicCharacteristics
Characteristic, n (%)
Arm ICP
(n=625)
Arm IICP + BEV(n=625)
Arm IIICP + BEV BEV
(n=623)
Stage/residual size
III optimal (macroscopic) 218 (35) 205 (33) 216 (35)
III suboptimal 254 (41) 256 (41) 242 (39)
IV 153 (25) 164 (26) 165 (27)
Histology
Serous 543 (87) 523 (84) 525 (84)
Endometrioid 20 (3) 15 (2) 25 (4)
Clear cell 11 (2) 23 (4) 18 (3)
Mucinous 8 (1) 5 (<1) 8 (1)
Tumor grade
3a 412 (66) 435 (70) 430 (69)
2 94 (15) 77 (12) 92 (15)
1 33 (5) 28 (4) 16 (3)
Not specified/pending 86 (14) 85 (14) 85 (14)
Percentages may not total 100% due to rounding or categorizationaGrade 3 includes all clear cell tumors
GOG-0218: Baseline Surgical–PathologicCharacteristics
Characteristic, n (%)
Arm ICP
(n=625)
Arm IICP + BEV(n=625)
Arm IIICP + BEV BEV
(n=623)
Stage/residual size
III optimal (macroscopic) 218 (35) 205 (33) 216 (35)
III suboptimal 254 (41) 256 (41) 242 (39)
IV 153 (25) 164 (26) 165 (27)
Histology
Serous 543 (87) 523 (84) 525 (84)
Endometrioid 20 (3) 15 (2) 25 (4)
Clear cell 11 (2) 23 (4) 18 (3)
Mucinous 8 (1) 5 (<1) 8 (1)
Tumor grade
3a 412 (66) 435 (70) 430 (69)
2 94 (15) 77 (12) 92 (15)
1 33 (5) 28 (4) 16 (3)
Not specified/pending 86 (14) 85 (14) 85 (14)
Percentages may not total 100% due to rounding or categorizationaGrade 3 includes all clear cell tumors
GOG-0218: Patient Disposition
Characteristic
Arm ICP
(n=625)
Arm IICP + BEV(n=625)
Arm IIICP + BEV BEV
(n=623)
Median (range) number BEV/placebo cycles 11 (0–22a) 12 (0–22a) 14 (0–21)
On treatment at time of analysis, n (%) 86 (14) 82 (13) 117 (19)
Completed regimen, n (%) 100 (16) 104 (17) 148 (24)
Discontinued study treatment, n (%)
Disease progression 299 (48) 264 (42) 164 (26)
Adverse events 69 (11) 86 (14) 94 (15)
Cycles 1–6 57 (9) 73 (12) 59 (9)
Cycle ≥7 12 (2) 13 (2) 35 (6)
Deaths 8 (1) 7 (1) 13 (2)
Patient refusal 44 (7) 55 (9) 50 (8)
Other 19 (3) 27 (4) 37 (6)
aOne patient in each group received BEV/placebo in cycle 1Percentages may not total 100% due to rounding or categorization
Adverse event (grade when limited), n (%)
Arm ICP
(n=601)
Arm IICP + BEV(n=607)
Arm IIICP + BEV BEV
(n=608)
GI eventsa (grade ≥2) 7 (1.2) 17 (2.8) 16 (2.6)
Hypertension (grade ≥2) 43 (7.2)b 100 (16.5)b 139 (22.9)b
Proteinuria (grade ≥3) 4 (0.7) 4 (0.7) 10 (1.6)
Pain (grade ≥2) 250 (41.7) 252 (41.5) 286 (47.1)
Neutropenia (grade ≥4) 347 (57.7) 384 (63.3) 385 (63.3)
Febrile neutropenia 21 (3.5) 30 (4.9) 26 (4.3)
Venous thromboembolic event 35 (5.8) 32 (5.3) 41 (6.7)
Arterial thromboembolic event 5 (0.8) 4 (0.7) 4 (0.7)
CNS bleeding 0 0 2 (0.3)
Non-CNS bleeding (grade ≥3) 5 (0.8) 8 (1.3) 13 (2.1)
RPLS 0 1 (0.2) 1 (0.2)
GOG-0218: Select Adverse EventsOnset between cycle 2 and 30 days after date of last treatment
RPLS = reversible posterior leukoencephalopathy syndromeaPerforation/fistula/necrosis/leak
bp<0.05
GOG-0218: Investigator-Assessed PFSArm I
CP (n=625)
Arm IICP + BEV(n=625)
Patients with event, n (%)423
(67.7)418
(66.9)
Median PFS, months 10.3 11.2
Stratified analysis HR (95% CI)
0.908(0.759–1.040)
One-sided p-value (log rank) 0.080a
+ BEV (Arm II)CP (Arm I)
ap-value boundary = 0.0116
+ BEV → BEV maintenance (Arm III)Pro
po
rtio
n s
urv
ivin
g p
rog
ress
ion
fre
e
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
Arm IIICP + BEV BEV
(n=623)
360 (57.8)
14.1
0.717 (0.625–0.824)
<0.0001a
Burger et al. NEJM 2011;365 (26):2473–83© Massachusetts Medical Society
GOG-0218: subgroup analyses of PFSRisk factor Total no. of patients Hazard ratio for Avastin (95% CI)
Cancer stage and residual lesion size III, macroscopic ≤1cm Arm II vs Arm I Arm III vs Arm I
423 434
0.7800.618
III, >1cm Arm II vs Arm I Arm III vs Arm I
510 496
0.9810.763
IV Arm II vs Arm I Arm III vs Arm I
317 318
0.9230.698
Histologic type
Serous Arm II vs Arm I Arm III vs Arm I
1,0661,068
0.9130.701
Nonserous Arm II vs Arm I Arm III vs Arm I
184 180
0.8930.713
Tumour grade
1 or 2 Arm II vs Arm I Arm III vs Arm I
232 235
1.0390.578
3 Arm II vs Arm I Arm III vs Arm I
847 842
0.8910.700
0.33 0.50 0.67 1.00 1.50 2.00 3.00
bevacizumab better Control better
Burger et al. NEJM 2011;365 (26):2473–83© Massachusetts Medical Society
GOG-0218: subgroup analyses of PFS (cont’d)
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:
• PFS hazard ratio (HR) of 0.78
• Increase of median PFS from 18 to 23 months
• Secondary endpoints: Overall survival (due 2012), response rate, toxicity
• Substudies: Quality of life, health economics, translational research
30
Baseline characteristics (1)
CharacteristicControl (n=764)
Research (n=764)
Median age (range) 57 (18–81) 57 (24–82)
ECOG PS, n (%) 0 1 2
358 (47)354 (47)
43 (6)
334 (45)366 (49)45 (6)
Origin of cancer, n (%) Ovary (epithelial) Fallopian tube Primary peritoneal Multiple sites
667 (87)29 (4)56 (7)12 (2)
673 (88)27 (4)50 (6)14 (2)
Histology Serous Clear cell Endometrioid Mucinous Mixed/other
529 (69)60 (8)57 (7)15 (2)
103 (13)
525 (69)67 (9)60 (8)19 (2)
93 (12)
Grade, n (%) 1 2 3 Unknown
56 (7)142 (19)556 (74)
10
41 (5)175 (23)538 (71)
10
31
Baseline characteristics (2)
Characteristic, n (%)Control (n=764)
Research (n=764)
FIGO stage, n (%) I/IIA IIB–IIIB IIIC/IV
75 (10)160 (21)529 (69)
67 (9)155 (20)542 (71)
Debulking surgery/residuum Optimal surgery (≤1 cm) Suboptimal surgery (>1 cm) No surgery
552 (74)195 (26)17 (2)
559 (74)192 (26)13 (2)
FIGO stage and residuum* Stage I–III (≤1 cm) Stage I–III (>1 cm) Stage III (inoperable)/IV
508 (66)150 (20)106 (14)
518 (68)140 (18)106 (14)
Intent to start chemotherapy* ≤4 weeks from surgery >4 weeks from surgery
328 (43)436 (57)
326 (43)438 (57)
32
*Stratification variable
Selected adverse events (all grades)
6.2
2.5 2.1 1.3 0.4
11.6
4.11.5 0.4 0
29.1
2.0
9.2
25.9
4.4 5.0
1.7 1.3
39.6
6.73.6
0.4 0
28.3
2.8
12.5
0
5
10
15
20
25
30
35
40
45Control (n=753)
Research (n=745)
ATE = arterial thromboembolism; CHF = congestive heart failure; RPLS = reversible posterior leucoencephalopathy syndrome; VTE = venous thromboembolism
Pati
ents
(%
)Pati
ents
(%
)
33
2.10.1 0.4
0.90.4 0.3
1.7 1.3 0.4 0
15.1
2.0 2.0
18.3
0.5 1.3 0.8 1.3 1.2
4.32.7
0.3 0
16.5
2.6 3.5
0
5
10
15
20
25
30
35
40
45Control (n=753)
Research (n=745)
ATE = arterial thromboembolism; CHF = congestive heart failure; RPLS = reversible posterior leucoencephalopathy syndrome; VTE = venous thromboembolism
Pati
ents
(%
)Pati
ents
(%
)
34
Selected grade ≥3 adverse events
(gra
de ≥
2)
Number at riskControl 764 723 693 556 464 307 216 143 91 50 25Research 764 748 715 647 585 399 263 144 73 36 19
Number at riskControl 764 723 693 556 464 307 216 143 91 50 25Research 764 748 715 647 585 399 263 144 73 36 19
Progression-free survival
1.00
0.75
0.50
0.25
0
1.00
0.75
0.50
0.25
0
Pro
port
ion a
live w
ithout
pro
gre
ssio
nPro
port
ion a
live w
ithout
pro
gre
ssio
n
Time (months)Time (months)0 3 6 9 12 15 18 21 24 27 300 3 6 9 12 15 18 21 24 27 30
Control ResearchEvents, n (%) 392 (51) 367 (48)Median, months 17.3 19.0Log-rank test p=0.0041
HR (95% CI) 0.81 (0.70–0.94)
17.3 19.0
ControlResearch
Academic analysis
35
Number at riskControl 234 205 98 36 14 2Research 231 213 159 56 10 1
Number at riskControl 234 205 98 36 14 2Research 231 213 159 56 10 1
PFS: FIGO stage III suboptimal and FIGO stage IV with debulking
1.00
0.75
0.50
0.25
0
1.00
0.75
0.50
0.25
0
Pro
port
ion a
live w
ithout
pro
gre
ssio
nPro
port
ion a
live w
ithout
pro
gre
ssio
n
Time (months)Time (months)0 3 6 9 12 15 18 21 24 27 300 3 6 9 12 15 18 21 24 27 30
Control(n=234)
Research (n=231)
Events, n (%) 173 (74) 158 (68)
Median, months 10.5 15.9Log-rank test p<0.001
Hazard ratio (95% CI) 0.68 (0.55–0.85)
Restricted mean 13.3 16.5
10.5 15.9
ControlResearch
37
No. of events/no. of patients
Origin of cancerCP + Av7.5
Av7.5CP HR
Age <60 202/449 210/450 0.84
60–69 134/242 142/237 0.76
≥70 31/73 40/77 0.82
ECOG PS 0 154/334 145/358 1.01
1 175/366 210/354 0.66
2 27/45 31/43 0.78
Histology Serous 274/525 278/529 0.85
Mucinous 12/19 10/15 0.77
Endometroid 26/60 25/57 0.81
Clear cell 22/67 22/60 0.90
Hazard ratio (fixed)
0 1 20.5 1.5
CP + Bev7.5 Bev 7.5 better CP better
Age: Trend p=0.69, interaction p=0.83 ECOG: Trend p=0.027, interaction p=0.022Histology: Interaction test p=0.085
Perren et al. NEJM 2011;365 (26):2482–2496© Massachusetts Medical Society
Subgroup analysis of PFS (1)
FIGO: Trend p=0.71, interaction p=0.91Residual disease: Trend p=0.10Grade: Trend p=0.76, interaction p=0.95
Perren et al. NEJM 2011;365 (26):2482–2496© Massachusetts Medical Society
Subgroup analysis of PFS (2)
No. of events/no. of patients
Origin of cancerCP + Av7.5
Av7.5CP HR
FIGO I 6/54 9/65 0.73
II 14/83 19/80 0.72
III 277/523 290/522 0.79
IV 70/104 74/97 0.69
Residual disease
Optimal (≤1cm) 226/559 233/552 0.87
Suboptimal (>1cm) 131/192 145/195 0.68
Grade Grade 1 10/41 16/56 0.76
Grade 2 86/175 77/142 0.77
Grade 3 267/538 294/556 0.81
Hazard ratio (fixed)
0 1 20.5 1.5
CP + Bev7.5 Bev7.5 better CP better
Perren et al. NEJM 2011;365 (26):2482–2496© Massachusetts Medical Society
Interim OS analysis, full population (regulatory request)
1.00
0.75
0.50
0.25
0
1.00
0.75
0.50
0.25
0
Pro
por
tion
aliv
eP
rop
ortio
n al
ive
Time (months)Time (months)0 3 6 9 12 15 18 21 24 27 30 33 36 390 3 6 9 12 15 18 21 24 27 30 33 36 39
Number at riskCP 764 741 724 703 672 646 623 542 421 304 212 132 71 26CP + Av7.5 764 753 737 717 702 680 657 592 459 329 228 129 69 19 Av7.5
Number at riskCP 764 741 724 703 672 646 623 542 421 304 212 132 71 26CP + Av7.5 764 753 737 717 702 680 657 592 459 329 228 129 69 19 Av7.5
CPCP + Av7.5 Av7.5
Deaths, n (%) 200 (26) 178 (23)
Median, months Not yet reached
Log-rank test p=0.11
HR (95% CI) 0.85 (0.69–1.04)
1-year OS rate (%) 92 95
Number at riskCP 234 219 194 166 107 46 15CP + Av7.5 231 222 208 186 134 65 18 Av7.5
Number at riskCP 234 219 194 166 107 46 15CP + Av7.5 231 222 208 186 134 65 18 Av7.5
High-risk subgroup
CP (n=234)
CP + Av7.5 Av7.5 (n=231)
Deaths, n (%) 109 (47) 79 (34)
Median, months 28.8 36.6
Log-rank test p=0.002
HR (95% CI) 0.64 (0.48–0.85)
1-year OS rate (%) 86 92
Perren et al. NEJM 2011;365 (26):2482–2496© Massachusetts Medical Society
OS: high-risk patients (FIGO stage III suboptimal and FIGO stage IV with debulking)
1.00
0.75
0.50
0.25
0
1.00
0.75
0.50
0.25
0
Time (months)Time (months)0 3 6 9 12 15 18 21 24 27 30 33 36 390 3 6 9 12 15 18 21 24 27 30 33 36 39
Pro
por
tion
aliv
eP
rop
ortio
n al
ive
Data cut-off date: November 30, 2010Perren et al. NEJM 2011;365 (26):2482–2496
© Massachusetts Medical Society
Updated PFS
CP
CP + Av7.5 Av7.5
Events, n (%) 464 (61) 470 (62)
Median, months 17.4 19.8
Log-rank test p=0.04
HR (95% CI) 0.87 (0.77–0.99)
Pro
por
tion
aliv
e w
ithou
t pr
ogre
ssio
nP
rop
ortio
n al
ive
with
out
prog
ress
ion
Time (months)Time (months)
17.4 19.8
764764
693716
474599
350430
221229
114107
3927
Number at riskCPCP + Av7.5 Av7.5
Number at riskCPCP + Av7.5 Av7.5
0 3 6 9 12 15 18 21 24 27 30 33 360 3 6 9 12 15 18 21 24 27 30 33 36
1.00
0.75
0.50
0.25
0
1.00
0.75
0.50
0.25
0
Conclusions Bevacizumab combined with chemotherapy and
continued alone (7.5 mg/kg for 12 months) vs chemotherapy demonstrates
Continued improvement in PFS with no crossing of curves
Trend for improved OS continues in the total population
Final analysis of OS is due in 2013
Treatment effect is greater in patients at high risk of recurrence, which may be of clinical relevance
Perren, et al. NEJM 2011
Take Home Messages
1) MITO-2: carboplatina/doxil: considerado um
esquema padrão de 1o linha alternativo para
pacientes com neuropatia e para aqueles que
querem evitar alopécia
2) GOG 218 e ICON 7:
carboplatina/paclitaxel/bevacizumabe (indução e
manutenção) considerado uma opção de 1o linha
em pacientes selecionadas
Obrigado
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