Ovarian Cancer: A new look at an old veteran - PowerPoint PPT Presentation

Loading...

PPT – Ovarian Cancer: A new look at an old veteran PowerPoint presentation | free to download - id: 7720bb-MjZjZ



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Ovarian Cancer: A new look at an old veteran

Description:

Ovarian Cancer: A new look at an old veteran Sana Al-Sukhun, MD, MSc. Assistant Professor, Medical Oncology/ Hematology University of Jordan Best of ASCO – PowerPoint PPT presentation

Number of Views:12
Avg rating:3.0/5.0
Slides: 31
Provided by: Asco47
Learn more at: http://www.lsmo-lb.org
Category:
Tags: alberts | cancer | look | new | old | ovarian | veteran

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Ovarian Cancer: A new look at an old veteran


1
Ovarian CancerA new look at an old veteran
Sana Al-Sukhun, MD, MSc. Assistant Professor,
Medical Oncology/ Hematology University of Jordan
Best of ASCO July 11th 2009
2
Ovarian Cancer
  • First line treatment
  • Standard Tx Carboplatin / paclitaxel.
  • Relapsed setting
  • Choice of relapsed disease treatment is dependent
    on interval since prior platinum-based therapy
  • Relapse within 6 months platinum-resistant
    disease
  • Relapse over 6 months platinum-sensitive disease
  • Carboplatin-paclitaxel is standard in
    platinum-sensitive disease

Ozols RF et al, J Clin Oncol 2003, 21
3194-3200
3
ASCO conflict of interest statement
  • MITO-2 is an independent, academic study.
  • Sponsor of the study is NCI Naples, that is
    responsible for trial design, study coordination,
    data analysis and has the property of the
    database.
  • The study was partially supported by funds from
    Schering-Plough.
  • Schering-Plough Italy supplied pegylated
    liposomal doxorubicin (PLD).
  • Sandro Pignata received honoraria from
    Schering-Plough.

4
Introduction
  • Carboplatin plus paclitaxel is standard
    first-line chemotherapy for patients with
    advanced ovarian cancer 1-3
  • Single-agent pegylated liposomal doxorubicin
    (PLD) is a standard option for platinum resistant
    relapsed ovarian cancer 4
  • 1Ozols RF et al, J Clin Oncol 2003, 21
    3194-3200
  • 2Neijt JP et al , J Clin Oncol 2000, 18
    3084-3092
  • 3du Bois A et al , J Natl Cancer Inst 2003,
    951320-1330
  • 4Gordon AN et al, J Clin Oncol 2001, 19
    3312-3322

5
Is carboplatin / liposomal doxorubicin a
replacement doublet for carboplatin / paclitaxel?
6
Introduction
  • Single-agent pegylated liposomal doxorubicin
    (PLD) is a standard option for platinum resistant
    relapsed ovarian cancer 1.
  • Combination of carboplatin and PLD is highly
    active as second-line chemotherapy in patients
    with advanced ovarian cancer in late relapse 2-3
  • 1Gordon AN et al, J Clin Oncol 2001, 19
    3312-3322
  • 2Ferrero JM et al, Proc Am Soc Clin Oncol 2002
  • 3Ferrero JM et al, Ann Oncol 2007, 18 263-268

7
Introduction
  • Combination of carboplatin and PLD is highly
    active as second-line chemotherapy in patients
    with advanced ovarian cancer in late relapse 1-2
  • 1Ferrero JM et al, Proc Am Soc Clin Oncol 2002
  • 2Ferrero JM et al, Ann Oncol 2007, 18 263-268

8
Carboplatin plus Paclitaxel versus Carboplatin
plus Stealth Liposomal Doxorubicin in patients
with advanced ovarian cancer activity and
safety results of the MITO-2 randomized
multicenter trial
  • S. Pignata1, G. Scambia2, A. Savarese3, R.
    Sorio4, E. Breda5,
  • G. Ferrandina2, V. Gebbia6, P. Musso7, C. Gallo8,
    F. Perrone9
  • 1Istituto Nazionale Tumori, Napoli 2Università
    Cattolica del Sacro Cuore, Roma 3Istituto Regina
    Elena, Roma
  • 4CRO, Aviano 5Ospedale Fatebenefratelli, Isola
    Tiberina, Roma
  • 6Casa di Cura La Maddalena, Università di
    Palermo 7Ospedale Oncologico M.Ascoli
    A.R.N.A.S., Palermo
  • 8Seconda Università di Napoli 9Istituto
    Nazionale Tumori di Napoli,Italy.

9
Study objective
  • MITO-2 is a randomized phase III study testing
    whether carboplatin plus PLD is more effective
    than carboplatin plus paclitaxel as first-line
    treatment of patients with advanced ovarian
    cancer

10
Study design
Control arm
Random
Carboplatin AUC 5, day 1 Paclitaxel 175 mg/m2,
day 1 Treatment repeated every 21 days, for 6
cycles
11
Experimental arm
Carboplatin AUC 5, day 1 PLD 30 mg/m2, day
1 Treatment repeated every 21 days, for 6 cycles
  • Strata
  • Center
  • PS (0-1, 2)
  • Stage (IC, II, III, IV)
  • Residual disease after surgery
  • (absent, ?1 cm, ?1 cm, no surgery)

11
Study design
Random
Control arm
Carboplatin AUC 5, day 1 Paclitaxel 175 mg/m2,
day 1
11
Experimental arm
Carboplatin AUC 5, day 1 PLD 30 mg/m2, day 1
Is carboplatin plus PLD more effective than
carboplatin plus paclitaxel as first-line
treatment of patients with advanced ovarian
cancer?
Objective To demonstrate improvement in PFS
from 18 to 22.5 months ( HR 0.8, 80 power).
12
Study population
  • Inclusion criteria
  • Cyto/histological diagnosis of ovarian cancer
  • FIGO Stage IC II III IV
  • Age ? 75
  • ECOG Performance Status 0-2
  • No previous chemotherapy
  • Main exclusion criteria
  • ANC ? 2000/?L, platelets ? 100000/?L
  • Creatinine ? 1.25 x UNL, SGOT and SGPT ? 1.25 x
    UNL
  • Life expectancy of less than 3 months

13
Study endpoints
  • Primary endpoint
  • Progression-free survival (PFS)
  • Secondary endpoints
  • Overall survival (OS)
  • Objective response rate (RECIST)
  • Toxicity (NCI CTC v2.0)
  • Quality of Life (EORTC QLQ C30)

14
Sample size
  • 2-tailed ? 0.05
  • Power 80
  • Hazard Ratio 0.80
  • Median PFS in control arm 18 months
  • Median PFS in experimental arm 22.5 months
  • ? 632 events (progressions) needed
  • ? 820 patients planned

15
Study conduction
  • First patient enrolled January 17, 2003
  • Last patient enrolled November 9, 2007
  • 42 active Institutions (41 Italy, 1 Portugal)
  • 820 randomized pts (809 Italy, 11 Portugal)
  • Preplanned early safety analysis
  • first 50 pts receiving carboplatin PLD 1
  • Preplanned interim activity analysis
  • first 50 pts eligible for RECIST assigned to
    carboplatin PLD 2
  • 1Pignata S, BMC Cancer 2006 6 202
  • 2Pignata S, Oncology 2009 76 49-54

16
Baseline characteristics
Carbo Paclitaxel Carbo Paclitaxel Carbo PLD Carbo PLD
(n 410) (n 410) (n410) (n410)
Age median (range) 57 (21-77) 57 (25-77)
ECOG Performance Status ECOG Performance Status ECOG Performance Status
0-1 398 (97) 397 (97)
2 12 (3) 13 (3)
FIGO Stage
IC 38 (9) 38 (9)
II 40 (10) 37 (9)
III 243 (59) 247 (60)
IV 89 (22) 88 (22)
Residual disease after surgery Residual disease after surgery Residual disease after surgery
Absent 152 (37) 150 (37)
? 1 cm 68 (17) 69 (19)
? 1 cm 117 (28) 114 (28)
No surgery 73 (18) 67 (16)
17
Treatment compliance
Carbo Paclitaxel Carbo PLD Carbo PLD
(n 410) (n410) (n410)
Pending information 29 (7) 27 (7) 27 (7)
Did not start treatment 4 (1) 6 (1) 6 (1)
Number of cycles received Number of cycles received Number of cycles received Number of cycles received
1 10 (3) 10 (3) 11 (3)
2 13 (3) 13 (3) 19 (5)
3 8 (2) 8 (2) 13 (4)
4 6 (2) 6 (2) 11 (3)
5 10 (3) 10 (3) 14 (4)
6 330 (88) 330 (88) 309 (82)
p0.39
18
Treatment compliance delays
Carboplatin Paclitaxel
Carboplatin PLD
Delays due to non hematologic toxicity
Number of patients
Delays due to hematologic toxicity
Cycle 2
Cycle 3
Cycle 4
Cycle 5
Cycle 6
Completed 6 cycles 82 Carboplatinum / PLD
Vs
88 receiving Carboplatinum / Paclitaxel P
0.39
19
Toxicity (1)
Any grade Any grade Any grade Severe (G?3) Severe (G?3) Severe (G?3)
CP CPLD p CP CPLD p
Toxic deaths 0.8 0.5 1
Anemia 59 68 0.007 4 10 ?0.001
RBC transfusions 2 6 0.002
Neutropenia 73 80 0.04 49 43 0.09
Febrile neutropenia 2 1 0.21
Thrombocytopenia 19 48 ?0.001 2 16 ?0.001
Platelet transfusions 0.3 2 0.06
Bleeding 0.3 1 0.37 - 1 0.24
CP carboplatin paclitaxel, 399 patients
CPLD carboplatin PLD, 386 patients
Chi square or Fisher exact test as appropriate
20
Toxicity (2)
Any grade Any grade Any grade Severe (G?3) Severe (G?3) Severe (G?3)
CP CPLD p CP CPLD p
Allergy 6 5 0.60 2 2 0.86
Heart 2 4 0.26 0.3 2 0.06
Fatigue 44 43 0.86 3 3 0.94
Constipation 32 32 0.99 1 1 0.73
Nausea 47 51 0.21 2 2 0.95
Vomiting 29 30 0.83 2 3 0.42
Diarrhoea 13 6 ?0.001 1 - 0.25
Hair loss 63 14 ?0.001
Skin toxicity 6 20 ?0.001 - 2 0.01
Stomatitis 9 20 ?0.001 0.3 0.5 0.62
Neurotoxicity 47 15 ?0.001 3 0.2 0.004
CP carboplatin paclitaxel, 399 patients
CPLD carboplatin PLD, 386 patients
Chi square or Fisher exact test as appropriate
21
Activity analysis flow of patients
Carbo Paclitaxel (n410)
Carbo PLD (n410)
18 pts
Pending information
10 pts

83 pts
88 pts
73 pts
Not eligible for RECIST
Non-target lesions only
Elevated CA-125 only
No lesions, normal CA-125

99 pts
80 pts
79 pts
Eligible for RECIST
156 (38)
134 (33)
Analysis performed according to intention to
treat principle
22
Objective response RECISTWomen with target
lesions
Carbo Paclitaxel (n156) Carbo PLD (n134) p (?2)
Objective response 92 (59) 76 (57) 0.70
Complete response 24 (15) 22 (16) 0.70
Partial response 68 (44) 54 (40) 0.70
No response 64 (41) 58 (43) 0.70
Stable disease 45 (29) 41 (31) 0.70
Progressive disease 9 (6) 7 (5) 0.70
Not evaluated 10 (6) 10 (7) 0.70
Objective response vs no response
23
Activity Women not eligible for RECIST
Carbo Paclitaxel Carbo PLD p (?2)
Non-target lesions only
Complete response (CR) 27 / 83 (33) 29 / 99 (29) 0.64
No CR / No PD 46 / 83 (55) 48 / 99 (48)
Progressive disease 2 / 83 (2) 4 / 99 (4)
Not evaluated 8 / 83 (10) 18 / 99 (18)
Elevated Ca125 only
Ca125 normalized 73 / 88 (83) 69 / 80 (86) 0.56
Complete response vs not Ca125 normalized vs
not
24
Primary endpoint
  • Number of events required for final analysis
    (632) has not been reached yet
  • As of May 4, 2009, with a median follow-up of 35
    months, 531 progressions have been recorded
  • Only overall curves are shown

25
Progression-free survival
Patients Events Median PFS (months) 1-yr PFS 2-yr PFS
820 531 17.7 (95CI 16.3-19.9) 65.0 41.9
Months
Patients at risk Patients at risk
820 531 258 134 69 21 -
May 2009
26
What have we learned?
  • Three weekly Carboplatinum / PLD is associated
    with
  • More delays- mainly due to hematological
    toxicity.
  • More skin toxicity and stomatitis.
  • Less hair loss and neurotoxicity.
  • RECIST response and complete remission
    similar.
  • PFS ?

27
What is the standard for platinum sensitive
relapse?

ICON 4 / OVAR 2.2
Platinum VS platinum / paclitaxel. Carboplatin
VS carboplatin / gemcitabine.
OVAR 2.5
28
CALYPSO trial
Carboplatin Pegylated Liposomal Doxorubicin
(PLD) versus Carboplatin Paclitaxel in
Relapsed, Platinum-sensitive Ovarian Cancer
Eric Pujade-Lauraine on behalf of all GCIG
collaborators
29
Carboplatin Pegylated Liposomal Doxorubicin
(PLD) versus Carboplatin Paclitaxel in
Relapsed, Platinum-sensitive Ovarian Cancer
CALYPSO trial
  • Eric Pujade-Lauraine
  • on behalf of all GCIG collaborators

30
Background
  • Despite response to 1st-line treatment, relapse
    is eventual for most patients with advanced
    ovarian cancer (AOC)
  • Choice of relapsed disease treatment is dependent
    on interval since prior platinum-based therapy
  • Relapse within 6 months platinum-resistant
    disease
  • Relapse over 6 months platinum-sensitive disease
  • Carboplatin-paclitaxel is standard in
    platinum-sensitive disease

31
Rationale for PLD-Carboplatin Doublet
  • Due to risk of cumulative neuropathy and of hair
    loss, other carboplatin combinations have been
    explored
  • Pegylated liposomal doxorubicin (PLD) is a
    rational choice for combined therapy
  • PLD outperformed topotecan in platinum-sensitive
    population in large randomized trial (significant
    benefit in PFS and OS)1,2
  • Phase II trial of PLD-carboplatin verified safety
    and efficacy3

1Gordon et al. J Clin Oncol. 2001193312-3322
2Gordon et al. ECCO 12. September 2003 (poster)
3Ferrero et al. Ann Oncol. 200718263-268.
32
CALYPSO Study Schema
International, Intergroup, Open-label, Randomized
Phase III Study
R A N D O M I Z E
Experimental arm CD PLD 30 mg/m2 IV d
1 Carboplatin AUC 5 d 1
Ovarian cancer in late relapse (gt 6 months) after
1st- or 2nd-line platinum-based therapy (previous
taxane required)
Q 28 days x 6 courses
Control arm CP Paclitaxel 175 mg/m2 IV d
1 Carboplatin AUC 5 d 1
  • Stratification
  • Therapy-free interval (6-12 mo vs gt 12 mo)
  • Measurable disease (yes vs no)
  • Center

Treatment continues longer if SD or Responsive.
Q 21 days x 6 courses
or progression in patients with SD or PR
33
CALYPSO Study Schema
NON-INFERIORITY study design
International, Intergroup, Open-label, Randomized
Phase III Study
R A N D O M I Z E
Experimental arm CD PLD 30 mg/m2 IV d
1 Carboplatin AUC 5 d 1
Ovarian cancer in late relapse (gt 6 months) after
1st- or 2nd-line platinum-based therapy (previous
taxane required)
Q 28 days x 6 courses
Control arm CP Paclitaxel 175 mg/m2 IV d
1 Carboplatin AUC 5 d 1
- Primary endpoint PFS. - Secondary
endpoints QOL OS
Q 21 days x 6 courses
or progression in patients with SD or PR
34
Key Eligibility Criteria
  • Age 18 years
  • ECOG performance status 2
  • Histologically proven diagnosis of cancer of the
    ovary, fallopian tube, or extra-ovarian papillary
    serous tumors
  • Disease progression gt 6 months after 1st- or
    2nd-line platinum-based therapy
  • Previous taxane exposure
  • Measureable disease (RECIST criteria) or CA 125
    assessable disease (GCIG criteria) or
    histologically proven diagnosis of relapse

35
Endpoints. Statistical discussions
  • Primary endpoint
  • Progression-free survival (PFS)
  • Statistical considerations
  • Two-arm, parallel, NON-INFERIORITY study design
  • Statistical assumptions based on PFS from
    ICON4/AGO-OVAR 2.2 trial1
  • Declare non-inferior if HR one-side 95 CI lt1.23
    (CDCP) for PFS
  • Power of 90 and one-sided confidence level of
    95
  • Number of events required 745

1Parmar et al. Lancet. 20033612099-2106.
36
Endpoints
  • Secondary endpoints
  • Qualitative and quantitative toxicities
  • Quality of life (EORTC QLQ-C-30 version 3.0 and
    OV-28 questionnaire version 1.0)
  • Overall survival (OS)

37
Accrual
N976
38
CALYPSO Worldwide Collaboration
Austria, Australia, Belgium, Canada, Denmark,
Finland, France, Germany, Italy, New Zealand,
Saudi Arabia, Spain, Sweden, Switzerland, Turkey
39
Accrual by Groups
317
227
137
76
71
60
49
22
17
40
Baseline Characteristics (1)
Characteristic CD (n466) CP (n508)
Characteristic Number of patients () Number of patients ()
Age, median ECOG performance status 0 1 2 Primary site of disease Ovarian Papillary/Serous histology Initial FIGO stage I/II III/IV Number of previous lines One Two 60.5 286 (61) 159 (34) 13 (3) 415 (89) 334 (72) 52 (11) 401 (86) 408 (88) 58 (12) 61.0 317 (62) 164 (32) 15 (3) 451 (89) 366 (72) 59 (12) 427 (84) 421 (83) 87 (17)
Missing values to attain 100.
41
Baseline Characteristics (2)
Characteristic CD (n466) CP (n508)
Characteristic Number of patients () Number of patients ()
Prior taxane Interval since prior therapy, median 6-12 months gt 12 months Measurable disease Yes No Tumour size lt 5 cm gt 5 cm Number of sites 1 gt 1 462 (99) 162 (35) 304 (65) 281(60) 185 (39) 377(81) 89(19) 217(47) 249 (53) 500 (99) 182 (36) 326 (64) 321 (63) 188 (37) 419 (82) 90 (18) 245(48) 264(52)
42
Treatment Feasibility
CD (n465) CP (n501)
Total treatment duration, median wk 21 16
Relative dose intensity Carbo 99PLD 99 Carbo 99Paclitaxel 98
Patients with 6 cycles, n () 395 (85) 392 (78)
Patients with 9 cycles, n () 36 (8) 36 (7)
Treatment discontinuation 70 (15) 110 (22)
Toxicity - related treatment discontinuation 27 (6) 73 (15)
Hypersensitivity reactions (5) (19)
Hypersensitivity - related discontinuation (1) (4)
Plt 0.001 Patients receiving at least one
cycle
43
Hematologic Toxicity
Toxicity, grade(gr) CD (n464) CP (n500) P Value
Toxicity, grade(gr) Number of patients () Number of patients () P Value
Neutropenia, gr 3 gr 4 144 (31) 20 (4) 121 (24) 108 (22) lt0.01
Febrile neutropenia, gr 3-4 10 (2) 21 (4) NS
Infection, gr 3-4 11 (3) 14 (3) NS
Thrombocytopenia, gr 3-4 73 (16) 31 (6) lt0.01
Bleeding, gr 3-4 3 (0.6) 0 (0) NS
Anemia, gr 3-4 37 (8) 27 (5) NS
NSnot significant.
44
Selected Non-Hematologic Toxicities During
Treatment
CD (n466) CD (n466) CP (n501) CP (n501)
Grade 2 Grade3/4 Grade 2 Grade 3/4
Nausea/vomiting 31 4 20 4
Constipation 19 2 20 2
Diarrhea 4 2 6 2
Arthralgia/myalgia 4 0 18 1
Hand-foot syndrome 11 2 2 0
Mucositis 13 2 6 1
Fatigue 31 7 34 7
Cardiac disorders 2 1 3 1
Plt 0.001
45
Selected Non-Hematologic Toxicities During
Treatment
Alopecia
CD (n466) CP (n501)
Alopecia grade 2 7 84
Plt 0.001
46
Long-Lasting Toxicity
CD (n466) CD (n466) CP (n501) CP (n501)
Grade 2 Grade 3/5 Grade 2 Grade 3/5
Neuropathy 4 1 24 4
Plt 0.001
47
Early Treatment Discontinuation
Reason CD (n466) CP (n501)
Reason Number of patients ( of total) Number of patients ( of total)
Toxicity Patient/investigator choice Progressive disease Intercurrent disease TOTAL 27 (6) 16 (3) 26 (6) 1 (lt1) 70 (15) 73 (15) 14 (3) 22 (4) 1 (lt1) 110 (22)
Plt 0.001
48
Carboplatin Hypersensitivity Reactions
CD (n466) CD (n466) CP (n501) CP (n501)
Grade 2 Grade 3/5 Grade 2 Grade 3/5
Hypersensitivity 3 2 10 9
One drug stopped - - 2 2
Both drugs stopped 1 1 4 4
Plt 0.001
Protocol included EORTC guidelines for
re-challenge after a hypersensitivity reaction to
carboplatin
49
Follow-up and Number of Events
  • Median follow-up 22 months
  • Number of events
  • Progressions or deaths 824 (85)
  • Deaths 322 (33)

50
Progression-Free Survival (ITT)
CD CP
Median PFS, mo 11.3 9.4
HR (95 CI) 0.82 (0.72, 0.94) 0.82 (0.72, 0.94)
Log-rank p-value (superiority) 0.005 0.005
P-value (non-inferiority) lt0.001 lt0.001
51
Combination chemotherapy for platinum sensitive
disease
52
Symmetry of Tumor Assessments
53
Sensitivity PFS analysis
54
Multivariate Analysis of Baseline Predictive
Factors on PFS
  • Significant predictors of PFS included

Baseline Factor Baseline Factor N Multivariate Cox Regression Model Multivariate Cox Regression Model Multivariate Cox Regression Model
Baseline Factor Baseline Factor N HR 95 CI P-value
Therapy-free interval 6-12 mo 342 1.00 (0.48, 0.65) lt 0.001
Therapy-free interval gt 12 mo 617 0.56 (0.48, 0.65) lt 0.001
Measurable Disease No 362 1.00 (1.27, 1.70) lt 0.001
Measurable Disease Yes 597 1.47 (1.27, 1.70) lt 0.001
CA 125 lt 100 316 1.00 (1.52, 2.07) lt 0.001
CA 125 100 643 1.77 (1.52, 2.07) lt 0.001
Treatment arm CP 499 1.00 (0.71, 0.93) 0.003
Treatment arm CD 460 0.80 (0.71, 0.93) 0.003
55
Key findings
  • In patients with platinum-sensitive relapsing
    ovarian cancer, the combination of
    PLD-carboplatin was not inferior in term of PFS
    to paclitaxel-carboplatin, and even was found
    significantly superior
  • 18 reduction in risk of recurrence (HR 0.82
    P0.005)
  • Overall survival data immature, with only 322
    deaths to date
  • Paclitaxel-carboplatin associated with more
    severe toxicity (carboplatin hypersensitivity),
    alopecia, and long-lasting toxicity (neuropathy)
  • Moderate reversible HFS, mucositis, and
    nausea/vomiting more frequent with PLD

56
Conclusions
  • Carboplatin-PLD demonstrated a superior
    therapeutic index (benefit/risk ratio) versus
    current standard, carboplatin-paclitaxel
  • PLD- carboplatin offers an evidence-based option
    for patients with platinum-sensitive recurrent
    ovarian cancer

57
Acknowledgement Patients and their families, and

GINECO AGO-OVAR NSGO
NCIC-CTG ANZGOG AGO-Austria
EORTC MITO MANGO
Study Office B. Votan G. Elser
G. Andersen M. Bacon J.
Martin B. Volger A.
Demeester J. Bryce R. Fossati N.
Le Fur P. Schantl C.
Jeppesen C. Goudreau K. Carlton
J. Ulmer Investigators
E. Pujade -Lauraine A. Lortholary F.
Joly B.Weber L. Gladieff A. Floquet R.
Largillier M. Fabbro A. Goupil R. Delva E.
Guardiola F. Priou G.De Rauglaudre D. Coeffic
E. Eisenhauer L. Elit P. Sauthier J. Bentley A.
Oza H. Chalchal A. Sugimoto M. Heywood P.
Bessette D. Popkin L. Kaizer W. Gotlieb P. Walde
G. Kristensen J. Kaern R. Sandvei J. Herrstedt E.
Aavall -Lundqvist T. Hogberg B. Lund K.
Boman H. Havsteen M. Hansen J. Maenpaa
J. Pfisterer J. Sehouli A. Du Bois P.
Wimberger B. Schmalfeldt J. Huober S. Mahner M.
Gropp M. Thill K. Baumann A. Burges A.
Staehle R. Kreienberg A. Belau M. Beckmann S.
Loibl A. Hasenburg G. Emons W. Aulitzky L.
Spaetling
C. Marth A. Zeimet A. Reinthaller L. Angleitner
-Boubenizek H. Schauer P. Sevelda E. Petru
I. Vergote N. Reed K. Van Eygen P. Ottevanger M.
Van der Burg A. Casado Herraez
S. Pignata G. Scambia R. Sorio E. Breda A. De
Matteis
A. Ferrero N. Colombo N. Donadello D. Gueli
Alletti A. Lissoni S. Siena
P. Vasey B. Fitzharris M. Buck T. Bonaventura M.
Vaughan M. Davy A. ODonnell C. Steer M. Quinn M.
Friedlander A. Goldrick F. Kirsten
Safety Office S. AzouzT. Tran
Coordinating Centre A. Bonvoisin E. Plançon F.
Pinot N. Chiannilkulchai
Supported by Shering Plough International S.
Stopatschinskaja C. Doherty B. Winograd
B. Hartley K. Djazouli
58
What have we learned?
  • Four weekly Carboplatinum / PLD is associated
    with
  • Less hematologic toxicity.
  • More skin toxicity and stomatitis.
  • Less hair loss and neurotoxicity.
  • The combination of PLD-carboplatin was not
    inferior in term of PFS to paclitaxel-carboplatin,
    BUT the question of superiority remains open.
  • 18 reduction in risk of recurrence (HR 0.82
    P0.005).
  • Overall survival data QOL pending.

59
Whats the implication?
  • Carboplatinum / PLD is associated with different
    toxicity profile from carboplatin/ paclitaxel.
  • More delays- mailnly due to hematologic toxicity.
  • More skin toxicity and stomatitis.
  • Less hair loss and neurotoxicity.
  • First line setting may be equivalent.
  • RECIST response and complete remission
    similar.
  • PFS ?

Discuss options with patient !
Three drugs did not improve PFS over
Carboplatinum / Paclitaxel.
60
No improvement in PFS with the addition of a
third cytotoxic to the standard regimen
Bookman MA et al, JCO 2009
61
No improvement in OS with the addition of a third
cytotoxic to the standard regimen
Bookman MA et al, JCO 2009
62
What have we learned?
Whats the implication?
  • Carboplatinum / PLD is associated with different
    toxicity profile from carboplatin/ paclitaxel.
  • More delays- mailnly due to hematologic toxicity.
  • More skin toxicity and stomatitis.
  • Less hair loss and neurotoxicity.
  • First line setting may be equivalent.
  • RECIST response and complete remission
    similar.
  • PFS ?
  • Relapsed setting . Definitely not inferior.

Discuss options with patient !
How does this compare to weekly Paclitaxel?
63

Isonishi et al, ASCO 2008
64
Thank You
Sana Al Sukhun, MD, MSc.
65
Overall survival
Patients Events Median OS (months) 1-yr OS 2-yr OS
820 269 56.3 (95CI 48.3-n.a.) 88.8 73.8
Months
Patients at risk Patients at risk
820 712 413 228 90 38 -
May 2009
66
Preliminary conclusions (1)
  • Toxicity profile of carboplatin plus PLD as
    first-line treatment of advanced ovarian cancer
    is markedly different from carboplatin plus
    paclitaxel
  • Carboplatin plus PLD is associated with
  • Higher incidence of anemia and thrombocytopenia
    (rarely requiring transfusions)
  • Higher incidence of stomatitis and cutaneous
    toxicity (that are rarely severe)
  • Lower incidence of hair loss and neurotoxicity

YES, Lower incidence of hair loss and
neurotoxicity
67
Preliminary conclusions (2)
  • There was no statistically significant difference
    in response rate between carboplatin plus PLD and
    carboplatin plus paclitaxel
  • Final analysis for the primary endpoint (PFS)
    will be performed as soon as the required number
    of events will be reached

68
Acknowledgements
  • All the patients and their families
  • The Investigators and the staff at each
    participating center

S.Pignata, S. Greggi, C.Pisano Napoli G.Scambia, D.Lorusso Roma F.Cognetti, A.Savarese Roma
A.Veronesi, R.Sorio Aviano V.Zagonel, E.Breda Roma G.Ferrandina Campobasso
V. Gebbia, R.Agueli Palermo C.Malzoni, A.Vernaglia Avellino L.Frigerio, L.Carlini Bergamo
M.Nardi, P.Del Medico Reggio C. P.Musso Palermo A.Febbraro, MC Merola Benevento
P.Scollo, G.Scibilia Cannizzaro E.Galligioni, V.Murgia Trento A.Gambi, S.Tamberi Faenza
A.Brandes, S.Rimondini Bologna A.Ravaioli, E.Pasquini Rimini N.Gebbia, MR.Valerio Palermo
E.Aitini, G.Cavazzini Mantova D.Natale, C.Chiapperino Penne F.Artioli, L.Scaltriti Carpi
V. Lorusso, A. Latorre Bari / Lecce AM.DArco, A. Fabbrocini Nocera Inf C.Gridelli, F.DelGaizo Avellino
B.Massidda, V.Pusceddu Cagliari S. De Placido, R. Lauria Napoli G.Lelli, M.Marzola - Ferrara
V.Fosser, R.De Vivo Vicenza S.Tumolo, M.Boccalon - Pordenone G.Giardina, S.Danese Torino
G.Colucci, E.Naglieri Bari D. Amadori, N. Riva Forlì A. De Matteis, E.Rossi Napoli
G.Lucarelli, G.Nettis Acquaviva d.F. T.Gamucci,M.Giampaolo - Frosinone S.Palazzo,R.Biamonte Cosenza
V.Montesarchio Napoli A.Cardone, G.Balbi Napoli G.Fasola, C.Sacco Udine
ML.Geminiani, V.Arigliano Budrio O.Campos, I.Henriques Coimbra, Portugal O.Campos, I.Henriques Coimbra, Portugal
Coordinating center F.Perrone, M.Di Maio, A.Morabito, E.De Maio, J.Bryce, G.Canzanella Napoli
Statistician center C.Gallo, G. Signoriello, P.Chiodini, N.Lama - Napoli
About PowerShow.com