Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer

• Published in: Gynecologic oncology Vol. 129; no. 3; pp. 452 - 458
• Main Authors: Armstrong, Deborah K., White, Allen J., Weil, Susan C., Phillips, Martin, Coleman, Robert L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2013
• Subjects: Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma, Ovarian Epithelial; Disease-Free Survival; Docetaxel; Drug Hypersensitivity - etiology; Fallopian Tube Neoplasms - drug therapy; Fallopian Tube Neoplasms - immunology; Farletuzumab; Female; Hematology, Oncology, and Palliative Medicine; Humans; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - immunology; Neoplasms, Glandular and Epithelial - drug therapy; Neoplasms, Glandular and Epithelial - immunology; Obstetrics and Gynecology; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - immunology; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - immunology; Platinum-sensitive; Taxane; Taxoids - administration & dosage; Taxoids - adverse effects; Carboplatin; Platinum-sensitive; Taxane; Farletuzumab; Ovarian cancer
• ISSN: 0090-8258; 1095-6859; 1095-6859
• DOI: 10.1016/j.ygyno.2013.03.002

Farletuzumab is a humanized monoclonal antibody to folate receptor-α, which is over-expressed in most epithelial ovarian cancers but largely absent on normal tissue. We evaluated clinical activity of farletuzumab, alone and combined with chemotherapy, in women with first-relapse, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancers. Fifty-four eligible subjects received open-label farletuzumab weekly, single agent or combined with carboplatin (AUC5–6) and taxane (paclitaxel 175mg/m2 or docetaxel 75mg/m2), every 21days for 6cycles, followed by farletuzumab maintenance until progression. Twenty-eight subjects with asymptomatic CA125 relapse received single-agent farletuzumab and could receive platinum/taxane chemotherapy plus farletuzumab after single-agent progression. Twenty-six subjects with symptomatic relapse entered the combination arm directly; 21 subjects entered after single agent. Primary endpoints included normalized CA125 and Overall Response Rate (ORR). Duration of each subject's second progression-free interval (PFI2) was compared with her own first response interval (PFI1). Farletuzumab was well-tolerated as single agent, without additive toxicity when administered with chemotherapy. Of 47 subjects who received farletuzumab with chemotherapy, 38 (80.9%) normalized CA125. In 9/42 (21%) evaluable subjects, PFI2 was≥PFI1, better than the historical rate (3%). There was a high response rate among subjects with PFI1 <12months (75%), comparable to that in subjects with PFI1 ≥12months (84%). Complete or partial ORR was 75% with combination therapy. Based on this study, farletuzumab with carboplatin and taxane may enhance the response rate and duration of response in platinum-sensitive ovarian cancer patients with first relapse after remission of 6–18months. •Complete or partial ORR was 75% with combination therapy.•Response rate among subjects with first progression-free interval <12months (75%) was comparable to subjects with progression-free interval ≥12 (84%).•In 21% of evaluable subjects, second progression-free interval was longer than first progression-free interval.