Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval.
BACKGROUND
OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L.P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6-12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy.


METHODS
a detailed analysis of subsequent therapies and survival outcomes in the overall population and in the subsets according to platinum sensitivity was therefore conducted.


RESULTS
similar proportions of patients received subsequent therapy in each arm (76% versus 77%), including further platinum-based regimens (49% versus 55%). Patients in the trabectedin/PLD arm received subsequent chemotherapy at a later time (median delay 2.5 months versus PLD arm). Overall survival from subsequent platinum was significantly prolonged in the partially platinum-sensitive disease subset (hazard ratio = 0.63; P = 0.0357).


CONCLUSIONS
the superiority of trabectedin/PLD over single-agent PLD in OVA-301 cannot be explained by differences in the extent or nature of subsequent therapies administered to these patients. On the other hand, these exploratory analyses support the hypothesis that the enhanced survival benefits in the partially platinum-sensitive subset might be due to an extended PFI leading to longer survival with subsequent platinum.
Kaye
S B
SB
Section of Medicine, Institute of Cancer Research, The Royal Marsden Hospital, Sutton, Surrey, UK. Electronic address: stan.kaye@rmh.nhs.uk.
Colombo
N
N
Medical Gynecologic Oncology Unit, European Institute of Oncology, Milan, Italy.
Monk
B J
BJ
Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University of California Irvine Medical Center, Orange, CA, USA.
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.
Vergote
I
I
Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University Hospital, Leuven, Belgium.
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, USA.
Santabárbara
P
P
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, USA.
Nieto
A
A
Clinical R&D and Medical Affairs Department, Pharma Mar, Madrid, Spain.
Poveda
A
A
Department of Medical Oncology, Valencian Institute of Oncology, Valencia, Spain.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004149:Dioxoles / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012008:Recurrence; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage; D000077606:Trabectedin; D016896:Treatment Outcome
D004149:Dioxoles; D009944:Organoplatinum Compounds; D044005:Tetrahydroisoquinolines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000077606:Trabectedin