Presentado Sabado 5 de Mayo :
Tolerability of long-term use of trabectedin (Tr) in combination with pegylated liposomal doxorubicin (PLD) in patients (pts) with relapsed ovarian cancer (ROC).
ABSTRACT 5121.
Author(s): I. Romero, N. Colombo, S. B. Kaye, J. Arranz, A. Roszak, D. M. Provencher, P. Santabarbara, E. Bayever, E. Almorin, F. Muggia; Instituto Valenciano de Oncologia, Valencia, Spain; University of Milan-Bicocca, Milan, Italy; The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom; Hospital General Universitario Gregorio Marañon, Madrid, Spain; Wielkopolsice Centrum Oncology, Poznan, Poland; CHUM-Hôpital Notre-Dame, Montreal, QC, Canada; PharmaMar, Colmenar Viejo, Madrid, Spain; Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ; New York University Medical Center, New York, NY
Abstract:
Background: OVA-301 was an open-label, multicenter, randomized phase III study comparing Tr+ PLD to PLD alone in 672 pts with ROC. The combination significantly improved PFS and RR, with a trend toward longer OS and manageable noncumulative toxicity (Monk, Ann Oncol 2008, Abs. LBA4). Protracted tolerability of Tr 1.1 mg/m2 and PLD 30 mg/m2, 3h-q3weeks vs. PLD 50 mg/m2 1.5h- q4weeks in pts receiving ≥6 cycles was analyzed. Methods: Safety evaluated in 320 (of 663 treated) pts receiving ≥ 6 cycles by adverse events (AEs), laboratory data and physical findings (NCI CTC Version 3.0).
Results: Baseline characteristics were balanced: median age 56 years (26-87); ECOG 0: 68%; median platinum-free interval: 9.2 months; prior taxanes: 78%; papillary/serous histology: 72%.
Conclusions: This novel nonplatinum, nontaxane combination is an efficacious regimen in pts with ROC with reasonable long-term tolerability in pts that received ≥ 6 cycles. Hematological toxicity and transaminase elevations were more common in the combination arm, yet transient, and not cumulative; and less frequent than at <6 cycles. HFS, mucosal inflammation, and stomatitis were more common with PLD. Discontinuation rates due to AEs were low. Updated data will be presented.
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Pts with ≥ 6 cycles Tr + PLD
(173 pts/1,580 cycles) PLD
(147 pts/1,224 cycles)
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Median cycles (range) 8 (6-21) 7 (6-22)
G3-4 hematologic AEs (per cycle) (%)
Neutropenia1/anemia/thrombocytopenia/
febrile neutropenia 40/4/5/1 17/1/1/<1
G3-4 transaminase elevations (per cycle) (%)2,3
AST/ALT 11/2 -/-
Any grade AEs (per cycle) (%)
Hand-foot syndrome(HFS)/mucosal inflammation/
stomatitis/hypersensitivity4 7/3/5/0.3 22/10/11/0.4
Supportive therapies (per cycle) (%)
G- CSF/antianemics 26/14 7/5
Reason for discontinuation (per pts)5
Drug-related AE (mainly neutropenia and
hand-foot syndrome) (%) 9 6
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1 Neutropenia more common at cycle <6 for both arms. 2 No hepatic failures. 3 In contrast to cycle <6: ALT, 95%; AST, 92%. 4 Only occurred in cycle 1-2. 5 Disease progression is most common reason for both arms.
One drug-related death with Tr+PLD: acute myeloid leukemia.