Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial.
BACKGROUND
OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD) over PLD alone in relapsed ovarian cancer. The optimal management of patients with partially platinum-sensitive relapse [6-12 months platinum-free interval (PFI)] is unclear.


METHODS
within OVA-301, we therefore now report on the outcomes for the 214 cases in this subgroup.


RESULTS
Trabectedin/PLD resulted in a 35% risk reduction of disease progression (DP) or death [hazard ratio (HR) = 0.65, 95% confidence interval (CI), 0.45-0.92; P = 0.0152; median progression-free survival (PFS) 7.4 versus 5.5 months], and a significant 41% decrease in the risk of death (HR = 0.59; 95% CI, 0.43-0.82; P = 0.0015; median survival 23.0 versus 17.1 months). The safety of trabectedin/PLD in this subset mimicked that of the overall population. Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), although patients in the trabectedin/PLD arm had a slightly lower proportion of further platinum (49% versus 55%). Importantly, patients in the trabectedin/PLD arm survived significantly longer after subsequent platinum (HR = 0.63; P = 0.0357; median 13.3 versus 9.8 months).


CONCLUSIONS
This hypothesis-generating analysis demonstrates that superior benefits with trabectedin/PLD in terms of PFS and survival in the overall population appear particularly enhanced in patients with partially sensitive disease (PFI 6-12 months).
Poveda
A
A
Area of Gynecologic Oncology, Valencian Institute of Oncology, Valencia, Spain. Electronic address: apoveda@fivo.org.
Vergote
I
I
Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospital, Leuven, Belgium.
Tjulandin
S
S
Department of Clinical Pharmacology and Chemotherapy, Russian Cancer Research Center, Moscow, Russia.
Kong
B
B
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan, Shandong, China.
Roy
M
M
Department of Gynecologic Oncology, University Hospital Center, Quebec, Canada.
Chan
S
S
Department of Clinical Oncology, Nottingham University Hospital, Nottingham, UK.
Filipczyk-Cisarz
E
E
Chemotherapy Department, Oncology Center, Wroclaw, Poland.
Hagberg
H
H
Department of Oncology, Akademiska Sjukhuset, Uppsala, Sweden.
Kaye
S B
SB
Department of Cancer Medicine, The Royal Mardsen Hospital, Sutton, Surrey, UK.
Colombo
N
N
Medical Gynecologic Oncology Unit, European Institute of Oncology, Milan, Italy.
Lebedinsky
C
C
Clinical R&D and Medical Affairs Department, Pharma Mar, Madrid, Spain.
Parekh
T
T
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ.
Gómez
J
J
Clinical R&D and Medical Affairs Department, Pharma Mar, Madrid, Spain.
Park
Y C
YC
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ.
Alfaro
V
V
Clinical R&D and Medical Affairs Department, Pharma Mar, Madrid, Spain.
Monk
B J
BJ
Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University of California Irvine Medical Center, Orange, CA, USA.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004149:Dioxoles / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000009:adverse effects; D000077606:Trabectedin; D016896:Treatment Outcome
D004149:Dioxoles; D009944:Organoplatinum Compounds; D044005:Tetrahydroisoquinolines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000077606:Trabectedin