Adverse event profile by therapy cycle for vintafolide plus pegylated liposomal doxorubicin (PLD) versus PLD alone in platinum-resistant ovarian cancer.

Gynecologic Cancer
Session Type and Session Title: 
General Poster Session, Gynecologic Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 5572)
James Thomas Symanowski, Elzbieta Kutarska, Mariusz Bidzinski, Binh Nguyen, Reshma A. Rangwala, R. Wendel Naumann; Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC; Centrum Onkologii Ziemi Lubelskiej, Doctor Directing Division, Department of Gynecology Oncology III, Lublin, Poland; Holycross Cancer Center, Department of Gynecological Oncology, Kielce, Poland; Endocyte, Inc., West Lafayette, IN; Merck, Whitehouse Station, NJ; Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC

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Abstract Disclosures


Background: Vintafolide (EC145), a folic acid/desacetylvinblastine conjugate, binds with high affinity to folate receptors expressed in epithelial ovarian cancers. This analysis evaluated the incidence of adverse events (AEs) by treatment cycle and as a percent of total treatment cycles administered in the PRECEDENT trial, a randomized open-label study of subjects with platinum-resistant ovarian cancer receiving either vintafolide+PLD or PLD alone. Methods: Women ≥18 years old with ECOG status 0-2 and exposure to ≤2 prior systemic cytotoxic regimens were randomized 2:1 to vintafolide (2.5 mg IV tiw, weeks 1 and 3, q28 days)+PLD (50 mg/m2 IV day 1, q28 days) or PLD alone (same dose + schedule). AEs in the safety population (received at least 1 dose of study drug) were evaluated by cycle. Results: 157 patients received a total of 720 treatment cycles (518 vintafolide+PLD, 202 PLD alone). AEs (all grades, vintafolide+PLD vs PLD alone): 85.9% and 80.2% of cycles. Anemia, neutropenia, and thrombocytopenia were observed in 16.6% (vs 10.4% administered PLD alone), 19.1% (vs 10.4%), and 2.7% (vs 3.0%) of all cycles, respectively. Febrile neutropenia was observed in 0.2% (vs 0.5%) of cycles, respectively. Stomatitis and hand-foot syndrome (HFS) occurred in 16.6% (vs 22.8%) and 19.1% (vs 15.8%) of cycles, respectively. Peripheral sensory, motor, or sensorimotor neuropathy or polyneuropathy occurred in 10.1% (vs 2.5%) of cycles, and constipation and small intestinal obstruction/ileus were observed in 12.7% (vs 10.4%) and 2.9% (vs 4.0%) of cycles, respectively. Fatigue was similar between arms—15.8% of vintafolide+PLD vs 14.9% of PLD cycles. All AEs were noncumulative except for HFS, which for both arms increased in frequency through Cycle 6 compared with Cycles 1 and 2. Grade 3/4 AEs (vintafolide+PLD vs PLD alone): 29.3% vs 18.3% of cycles. Conclusions: After the number of treatment cycles was accounted for, anemia, neutropenia, and neuropathy were numerically greater in patients on vintafolide+PLD. Thrombocytopenia, constipation, small intestinal obstruction/ileus, fatigue, and HFS were similar. Stomatitis was numerically greater in patients administered PLD alone. Clinical trial information: NCT00722592.