RANDOMIZED PHASE III TRIAL OF TRABECTEDIN VERSUS DOXORUBICIN-BASED CHEMOTHERAPY AS FIRST-LINE THERAPY IN TRANSLOCATION-RELATED SARCOMAS (TRS) Sant P. Chawla, Andrew Hendifar, Michael Leahy, Antoine Italiano, Shreyaskumar Patel, Peter Hohenberger, Armando Santoro, Arthur P. Staddon, Nicolas Penel, Sophie Piperno-Neumann, Pilar Lardelli, Antonio Nieto, Carmen Kahatt, Jean-Yves Blay
Randomized phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas (TRS). - PowerPoint PPT Presentation
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RANDOMIZED PHASE III TRIAL OF TRABECTEDIN VERSUS DOXORUBICIN-BASED CHEMOTHERAPY AS FIRST-LINE THERAPY IN TRANSLOCATION-RELATED SARCOMAS (TRS)
Sant P. Chawla, Andrew Hendifar, Michael Leahy, Antoine Italiano, Shreyaskumar Patel, Peter Hohenberger, Armando Santoro, Arthur P. Staddon, Nicolas Penel, Sophie Piperno-Neumann, Pilar Lardelli, Antonio Nieto, Carmen Kahatt, Jean-Yves Blay
Study Design An adaptive design in chemonaïve patients with advanced TRS, stratified by performance status and subtype, then randomized to receive:
Trabectedin: 1.5 mg/m2 in 24h iv infusion q3wk Doxorubicin based chemotherapy (DXCT): single agent
75 mg/m2 q3wk, or 60 mg/m2 combined with ifosfamide 6-9 g/m2 q3wk
MRCL (n= 40) Other TRS (n= 40)
RANDOMIZATION (1:1)
Eligible patients
PS= 0 PS= 1-2 PS= 0 PS= 1-2
Study Objectives Primary: Progression free survival (PFS) of trabectedin vs DXCT Secondary:
PFS at 6 months Response rate (RR) Overall survival Safety
PFS/RR analyzed by investigator assessment for all randomized patients
PFS/RR analyzed by independent review only for confirmed TRS patients
Results: Baseline Characteristics
Trabectedin (n=61) DXCT (n=60)
Age (yr) Median (range) 47 (19-78) 49 (19-78)
Sex Male / female 36 (59%) / 25 (41%) 38 (63%) / 22 (37%)
ECOG PS 0 28 (46%) 29 (48%)
1 32 (52%) 30 (50%)
2 1 (2%) 1 (2%)
Sarcoma type by Investigator
MRCL 28 (46%) 28 (47%)
Other 33 (54%) 32 (53%)
Sarcoma type by central pathology
MRCL 23 (38%) 17 (28%)
Other 28 (46%) 20 (33%)
Not confirmed* 10 (16%) 23 (38%)
* Wrong diagnosis 4 (7%) and 9 (15%) patients of the trabectedin and DXCT arms, no evidence of translocation in 3 (5%) and 2 (3%) patients, and lack of
available material for central review in 3 (5%) and 12 (20%) patients
Histology According Central Diagnosis (TRS Confirmed Patients N=88)
Summary The study was underpowered to detect any statistical
significant differences in the two arms due to high rate of censoring in both arms
Overall, no statistically significant differences in PFS/OS were observed
Median PFS was 19 mo. in trabectedin arm vs. 8 mo. in DXCT arm Median OS was 39 mo. in trabectedin arm vs. 27 mo. in DXCT
arm Safety profiles for trabectedin and DXCT were consistent with
previous studies Ability to administer trabectedin over prolonged periods
without cumulative toxicity may allow for longer disease control
Trabectedin should be further explored in a definitive randomized study in myxoid liposarcoma patients
BACK-UP SLIDES
Censoring ReasonsEfficacy population
Trabectedin (n=51) DXCT (n=37)
Surgery 12 (24%) 6 (16%)
Chemotherapy 6 (12%) 7 (19%)
Radiotherapy 3 (6%) 2 (5%)
Last tumor assessmenta 12 (24%) 5 (14%)
Otherb 2 (4%) 4 (11%)
Total 35 (69%) 24 (65%)
All randomized patients
Trabectedin (n=61) DXCT(n=60)
Surgery 11 (18%) 12 (20%)
Chemotherapy 5 (8%) 4 (7%)
Radiotherapy 3 (5%) 6 (10%)
Last tumor assessmenta 9 (15%) 6 (10%)
Otherb 4 (7%) 6 (10%)
Total 32 (52%) 34 (57%)a Patients on follow-up for disease assessment or with event/subsequent therapy out of study window or without PD at last tumor assessment available in database at cut-off date.b Censored at randomization (e.g.: untreated) or withdrawn due to related/unrelated adverse event or refusal before treatment onset/disease progression or new treatment out of study window.
Subsequent Chemotherapy Agents in Censored Patients
Trabectedin(n=35)
DXCT (n=24)
N % N %CEDIRANIB . . 1 4.2CYCLOPHOSPHAMIDE 2 5.7 2 8.3