1. nordic society of gynecologic oncology ( nsgo ) denmark, finland, norway, sweden
DESCRIPTION
A randomized, phase III study gemcitabine-paclitaxel-carboplatin (TCG) versus paclitaxel-carboplatin (TC) as first-line treatment of ovarian cancer: survival of FIGO stage I-IIA patients. - PowerPoint PPT PresentationTRANSCRIPT
A randomized, phase III study gemcitabine-paclitaxel-carboplatin (TCG) versus
paclitaxel-carboplatin (TC) as first-line treatment of ovarian cancer: survival of FIGO stage I-IIA
patients
1. Nordic Society of Gynecologic Oncology Nordic Society of Gynecologic Oncology ((NSGO))
Denmark, Finland, Norway, SwedenDenmark, Finland, Norway, Sweden
2. Arbeitsgemeinschaft Gynäkologische Arbeitsgemeinschaft Gynäkologische OnkologieOnkologie
((AGO) Studiengruppe Ovarialkarzinom) Studiengruppe Ovarialkarzinom
3. Groupe d’Investigateurs Nationaux pour Groupe d’Investigateurs Nationaux pour
l’Etudel’Etude des Cancers Ovariens (des Cancers Ovariens (GINECO), France), France
a GCIG Intergroup Studya GCIG Intergroup Study
Jørn Herrstedt1, Jens Huober2, Franck Priou3, Hans-Helge Müller2,
Mark Baekelandt1, Christian Kurzeder2, Jacobus Pfisterer2,
Anne Stähle2, Isabelle Ray-Coquard3, Andreas du Bois2 (PI).
ADDING A THIRD CYTOSTATIC DRUG TO TC RESULT
Triplet combination Gemcitabine AGO-GINECO-NSGO GOG-ANZGOG-MRC
Epirubicin1,2 AGO-GINECO NSGO-EORTC-NCIC-GEICO
Peg.-lip. Dox3 GOG-ANZGOG-MRC
Sequential doublet Gemcitabine3 GOG-ANZGOG-MRC
Topotecan3,4 NCIC-EORTC-GEICO
GOG-ANZGOG-MRC
Sequential single Topotecan5 AGO-GINECO
negative
negative
negative
negative
negative
?negative
1. du Bois A et al. J Clin Oncol 2006;24:1127-35.
2. Kristensen GB et al. J Clin Oncol 2004;22 (suppl):A5003
3. Bookman MA et al. J Clin Oncol 2009;27:1419-1425.
4. Hoskins PJ et al. J Clin Oncol 2008;26(suppl):LBA5505
5. Pfisterer J et al. JNCI 2006;98;1036-45.
RANDOMISATION
q 21 x 6
Paclitaxel 175 mg/m² d1
Carboplatin AUC 5 d1
q 21 x 6
Gemcitabine 800 mg/m² d1+8
Paclitaxel 175 mg/m² d1
Carboplatin AUC 5 d1
STUDY DESIGN
• Center
• Interval debulking surgery planned (yes/no)
• FIGO Stage and Tumor Residuals
•Stratum 1: FIGO IA/B G3 or IC – IIA
•Stratum 2:Stratum 2: FIGO IIB - IIIC + Tumor residual FIGO IIB - IIIC + Tumor residual << 1 cm 1 cm
•Stratum 3: Stratum 3: FIGO IV or FIGO IV or Tumor residual > 1 cm Tumor residual > 1 cm
STRATIFICATION
1st ENDPOINT Overall Survival in stratum 2+3
2nd ENDPOINTS PFS in stratum 2+3
PFS and OS in stratum 1
PFS and OS in all strata
Response Rate
Toxicity (NCI/CTC grade 3/4)
EORTC QLQ-C 30 , QLQ-OV 28
ENDPOINTS
PATIENT CHARACTERISTICS
RECRUITMENT AND COHORTS
Number of patients
Recruitment 1742
Analysed for primary endpoint in stratum 2 + 3
1567
Analysed for secondary end-point in stratum 1
175
PATIENT CHARACTERISTICS (%)
ALL PATIENTS TC
N = 882
TCG
N = 860
AGE
(mean years) 58.0 58.2
PS
(ECOG 0/1) 91.5 92.3
STAGE I-IIA
(FIGO) IIB-III
IV
10.8
73.0
16.2
10.5
73.1
16.4
PATIENT CHARACTERISTICS (%)
STRATUM 1 TC
N = 89
TCG
N = 86
AGE
(mean years) 56.1 55.9
PS
(ECOG 0/1) 95.5 98.8
STAGE IA
(FIGO) IB
IC
IIA
12.4
2.3
56.2
20.2
13.9
1.2
60.5
19.8
PATIENT CHARACTERISTICS (%)
ALL PATIENTS TC
N = 882
TCG
N = 860
HISTOLOGY
SEROUS
ENDOMETROID
MUCINOUS
73.7
9.1
4.2
75.1
7.7
3.8
TUMOR POST OP.
UNKNOWN
MICRO OR 0 CM
0.1-1 CM
> 1 CM
9.0
39.2
25.3
26.5
9.0
39.0
24.1
28.0
STRATUM 1 TC
N = 89
TCG
N = 86
HISTOLOGY
SEROUS
ENDOMETROID
MUCINOUS
55.1
16.9
9.0
54.7
20.9
9.3
TUMOR POST OP.
UNKNOWN
MICRO OR 0 CM
0.1-1 CM
> 1 CM
3.3
89.9
4.5
2.3
1.1
95.4
1.2
2.3
PATIENT CHARACTERISTICS (%)
FEASIBILITY
ALL PATIENTS TC
N = 882
TCG
N = 860
At least 1 course 874 850
> 6 courses 88.0% 87.2%
< 6 courses 12.0% 12.8%
FEASIBILITY
STRATUM 1 TC
N = 89
TCG
N = 86
At least 1 course 89 84
> 6 courses 93.3% 86.9%
< 6 courses 6.7% 13.1%
DOSE DEVIATIONS (%)
ALL PATIENTS TC
N = 882
TCG
N = 860
Interval 28+ days 7.5 11.6
P < 0.0001
> 1 dose reduction on day 1
1.9 3.4P < 0.0001
Dose omission gemcitabine day 8
--- 46.8
DOSE DEVIATIONS (%)
STRATUM 1 TC
N = 89
TCG
N = 86
Interval 28+ days 5.7 8.0
P = 0.1834
> 1 dose reduction on day 1
1.0 1.9P < 0.0001
Dose omission gemcitabine day 8
--- 40.6
RESULTS
STRATUM 1
0
0,25
0,5
0,75
1
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84
PROGRESSION-FREE SURVIVAL (RECIST & CA125) BY THERAPY: STRATUM 1 (FIGO I-IIA)
Patients at risk
TCTC 89 pts. / 21 evts.89 pts. / 21 evts. median - mos.median - mos.
TCGTCG 86 pts. / 17 evts.86 pts. / 17 evts. median - mos.median - mos.P
r o
b a
b i
l i
t y
[[monthsmonths]]
HR = 0.85 [95% CI: 0.45-1.61]
p = 0.6199
89 87 82 79 75 67 62 57 46 29 17 5 1 0 0
86 79 76 75 72 67 58 51 46 33 15 4 2 0 0
0
0,25
0,5
0,75
1
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84
OVERALL SURVIVAL BY THERAPY STRATUM 1 (FIGO I-IIA)
89 88 85 81 79 75 73 69 56 41 23 6 1 0 0
86 80 79 78 75 72 67 58 52 38 19 4 2 0 0Patients at risk
TCTC 89 pts. / 5 evts.89 pts. / 5 evts.median - mos.median - mos.
TCGTCG 86 pts. / 10 evts.86 pts. / 10 evts.median - mos.median - mos.
P r
o b
a b
i l
i t
y
[[monthsmonths]]
HR = 2.19 [95% CI: 0.75-6.41]
p = 0.1419
RESULTS
STRATUM 2 +3
0
0,25
0,5
0,75
1
0 6 12 18 24 30 36 42 48 54 60 66 72
PROGRESSION-FREE SURVIVAL (RECIST & CA125) BY THERAPY: STRATUM 2+3 (FIGO IIB-IV)
[[monthsmonths]]793 699 511 351 270 225 191 152 95 43 14 2
774 685 483 307 228 185 155 116 72 36 12 2
Patients
at risk
HR = 1.17 [95% CI: 1.05-1.31]
Logrank test: p = 0.0065
TCTC 793 pts. / 588 evts.793 pts. / 588 evts. median 16.0 [14.9-17.4] mos.median 16.0 [14.9-17.4] mos.
TCGTCG 774 pts. / 629 evts.774 pts. / 629 evts. median 14.7 [14.0-15.9] mos.median 14.7 [14.0-15.9] mos.
OVERALL SURVIVAL BY THERAPY STRATUM 2+3 (FIGO IIB-IV)
0
0,5
1
0 6 12 18 24 30 36 42 48 54 60 66 72 78
P r
o b
a b
i l
i t
y
[[monthsmonths]]
TCTC 793 pts. / 401 evts.793 pts. / 401 evts. median 48.9 [43.1-51.2] mos.median 48.9 [43.1-51.2] mos.
TCGTCG 774 pts. / 404 evts.774 pts. / 404 evts. median 45.8 [40.0-49.5] mos.median 45.8 [40.0-49.5] mos.
HR = 1.03 [95% CI: 0.90-1.18]
p = 0.6955
Patients at risk
793 750 705 638 557 489 420 338 226 89 31 5774 740 693 628 554 484 411 322 208 87 28 5
TOXICITY
ALL PATIENTS
Anemia (5168/5067) 1.0 4.9 < .0001
Thrombocytopenia (5168/5068) 1.1 11.4 < .0001
Leukopenia (5168/5067) 9.3 28.3 < .0001
Neutropenia (4905/4882) 32.3 45.2 < .0001
Febrile Neutropenia (5115/5003) 0.4 1.2 < .0001
Inf. without Neutropenia (5122/5009) 0.7 0.9 0.2705
G-CSF 5.2 12.5 < .0001
EPO 5.6 12.3 < .0001
Antibiotics 3.2 5.3 < .0001
Blood Products 2.3 9.3 < .0001
HEMATOLOGICAL TOXICITIES Grade 3/4 WORST OF ALL COURSES
Toxicity (NTC/NTCG) TC TCG p-value
Fatigue Fatigue (865/840)(865/840) 7.17.1 10.510.5 .0125.0125
Nausea (865/841) 3.2 4.3 .2579
Constipation (865/841) 4.5 6.5 .0672
Neuropathy-motor (865/840) 2.2 3.0 .3139
Neuropathy-sensory (865/840) 6.5 7.4 .4655
Athralgia (865/840) 4.7 4.1 .4871
Myalgia (865/840) 4.7 3.6 .2281
Pain (865/842) 6.1 6.1 .9475
Alopecia grade 2 (859/827) 93.8 92.9 .4330
NON-HEMATOLOGICAL TOXICITIES Grade 3/4 WORST OF ALL COURSES
Toxicity (NTC/NTCG) TC TCG p-value
ADDING A THIRD CYTOSTATIC DRUG TO TC RESULT
Triplet combination Gemcitabine3 AGO-GINECO-NSGO GOG-ANZGOG-MRC
Epirubicin1,2 AGO-GINECO NSGO-EORTC-NCIC-GEICO
Peg.-lip. Dox3 GOG-ANZGOG-MRC
Sequential doublet Gemcitabine3 GOG-ANZGOG-MRC
Topotecan3,4 NCIC-EORTC-GEICO
GOG-ANZGOG-MRC
Sequential single Topotecan5 AGO-GINECO
negative
negative
negative
negative
negative
negativenegative
1. du Bois A et al. J Clin Oncol 2006;24:1127-35.
2. Kristensen GB et al. J Clin Oncol 2004;22(suppl)A5003.
3. Bookman MA et al. J Clin Oncol 2009;27:1419-1425.
4. Hoskins PJ et al. J Clin Oncol 2008;26(suppl)LBA5505.
5. Pfisterer J et al. JNCI 2006;98;1036-45.
AGO-OVAR Coordinating GroupA. Belau (Greifswald)A. Burges (München)U. Canzler (Dresden)A. du Bois - PI
(Wiesbaden)M. Gropp (Düsseldorf)P. Harter (Wiesbaden)V. Heilmann (Ulm)F. Hilpert (Kiel)J. Huober (Tübingen)Ch. Jackisch (Marburg)R. Kimmig (Essen)S. Loibl (Frankfurt)H.-J. Lück (Hannover)W. Meier (Düsseldorf)J. Pfisterer (Kiel)B. Richter (Radebeul)B. Schmalfeldt (München)W. Schröder (Bremen) J. Sehouli (Berlin)A. Stähle (Karlsruhe) U. Wagner (Marburg)K. Wollschlaeger (Magdeburg)
GINECOA.-C. Hardy-Besard (Saint-Brieuc)F. Joly (Caen)B. Weber (Nancy)E. Lévy (Paris)F. Priou (La-Roch-Sur-Yon)J.-P. Guastalla (Lyon) J. Plaza (Montbéliard)D. Berton-Rigaud (Nantes)S. Abadie-Lacourtoisie (Angers)C. Platini (Metz)F. Mefti (Saint-Cloud)K. Yakendji (Créteil)H. Bourgeois (Poitiers)L. Bastit (Rouen)P. Chinet-Charrot (Rouen)
E. Pujade-Lauraine –PI (Paris)
Statistics and Data management Study Office Monitoring
AGO-OVAR H.-H. Müller G. Elser, C. Ackermann P. Schantl, S. Oxe, S. BigusM. Hahmann, B. Aminossadati A. Igler, U. Weitzel F. Gottwald, S. Lang, H. Lüers
K. Friccius, B. Saile, C. Renné,
GINECO D. Paraiso, N. Le Fur C. Dumont-Puléo M. Bekhiti, S. Lahmar
NSGO R. DePont Christensen G. Andersen C. Ramstad, L. Rosquist,H. Holst
Supported by Eli Lilly and Company
NSGOJ. Herrstedt - PI (Herlev)G. Kristensen (Oslo)J. Kaern (Oslo)T. Skeie-Jensen (Oslo)E. Lorenz (Trondheim)K. Bertelsen (Odense)M. Mirza (Odense)J. Lindegaard (Aarhus)H. Havsteen (Aarhus)E. Aavall-Lundqvist (Stockholm)B. Tholander (Stockholm)M. Kalling (Lund)T. Høgberg (Linkøping)K. Boman (Umeaa)J. Mâenpââ (Tampere)S. Jelic (Beograd)Ljiljana Stamatovic (Beograd)I. Takac (Maribor)
Acknowledgement: Patients, all centres, IDMSC, and…