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Background: Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced epitope of the tumor-associated mucin-1 (TA-MUC1). This study aimed to evaluate the efficacy and safety of switch maintenance therapy with gatipotuzumab in patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer.Patients and methods: In this double-blind, randomized, placebo-controlled, phase II trial, patients with at least stable disease (SD) following chemotherapy were randomized 2:1 to receive intravenous gatipotuzumab (500 mg followed by 1700 mg 1 week later) or placebo every 3 weeks until tumor progression or unacceptable toxicity occurred. Stratification factors were the number of prior chemotherapy lines (2 versus 3-5), response versus SD after the most recent chemotherapy, and progression-free survival (PFS) <6 versus 6-12 months following the prior therapy. Primary endpoint was PFS according to modified immune-related RECIST 1.1 response criteria. Secondary endpoints were PFS at 6 months, safety, overall response rate, CA-125 progression, overall survival, quality of life, and pharmacokinetics.Results: Overall, 216 patients were randomized to gatipotuzumab (n = 151) or placebo (n = 65). Median PFS with gatipotuzumab was 3.5 months as compared with 3.5 months with placebo (hazard ratio 0.96, 95% confidence interval 0.69-1.33, P = 0.80). No advantage for gatipotuzumab over placebo was seen in the secondary efficacy endpoints or in any stratified subgroups. Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions being the most common adverse events.Conclusions: Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients.

Objectives Sorafenib, an oral multikinase inhibitor of the VEGFR/PDGFR/Raf/MEK/ERK pathway, has shown potential activity in patients with recurrent ovarian cancer (OC). One strategy to prolong disease control and survival in patients with OC is maintenance therapy after achieving a complete response. A double-blind, randomized, placebo-controlled, phase II study to assess the efficacy and safety of maintenance therapy with sorafenib in the treatment of OC is presented. Methods Patients with epithelial OC or primary peritoneal cancer in complete remission were randomized to sorafenib 400 mg BID or matching placebo. The primary endpoint was progression-free survival (PFS). Results Of 246 randomized patients, 93% had OC; baseline characteristics were balanced between treatment arms. There was no significant difference between sorafenib and placebo arms for PFS (median 12.7 vs 15.7 months; hazard ratio 1.09; 95% CI 0.72-1.63), although there was a notable imbalance in early censoring. The most common ≥ grade 3 adverse events (AEs) were hand-foot skin reaction (39.0% vs 0.8%) and rash (14.6% vs 0%). More patients receiving sorafenib versus placebo required dose reductions (67.5% vs 30.1%), resulting in a lower than planned median daily dose (median 584.6 vs 800.0 mg). Treatment with sorafenib was of shorter duration (median 17.6 vs 51.9 weeks) with more frequent discontinuations due to AEs (37.4% vs 6.5%). Conclusions Sorafenib 400 mg BID cannot be recommended as maintenance therapy for patients with OC in complete remission. Assessment of efficacy was limited by the high rate of dose reductions and early discontinuations. © 2013 Elsevier Inc.

Contains fulltext : 49733.pdf (publisher's version ) (Open Access), PURPOSE: This was a multinational, open-label, randomized phase III trial comparing yttrium-90-labeled murine HMFG1 (90Y-muHMFG1) plus standard treatment versus standard treatment alone in patients with epithelial ovarian cancer (EOC) who had attained a complete clinical remission after cytoreductive surgery and platinum-based chemotherapy. PATIENTS AND METHODS: In total, 844 International Federation of Gynecology and Obstetrics stage Ic to IV patients were initially screened, of whom 447 patients with a negative second-look laparoscopy (SLL) were randomly assigned to receive either a single dose of 90Y-muHMFG1 plus standard treatment (224 patients) or standard treatment alone (223 patients). Patients in the active treatment arm received a single intraperitoneal dose of 25 mg of 90Y-muHMFG1 (target dose 666 MBq/m2). The primary end point was length of survival; secondary end points included time to relapse and safety. The study had an 80% power to detect a 15% change in survival. RESULTS: After a median follow-up of 3.5 years (range, 1 to 6 years), 70 patients had died in the active treatment arm compared with 61 patients in the control arm. Cox proportional hazards analysis of survival demonstrated no difference between treatment arms. In the study drug arm, 104 patients experienced relapse compared with 98 patients in the standard treatment arm. No difference in time to relapse was observed between the two study arms. Active therapy was associated with occasional grade 3 or 4 thrombocytopenia and neutropenia and grade 1 or 2 GI symptoms, abdominal discomfort, arthralgia, and myalgia. CONCLUSION A single IP administration of 90Y-muHMFG1 to patients with EOC who had a negative SLL after primary therapy did not extend survival or time to relapse.