Maintenance therapy of patients with recurrent epithelial ovarian carcinoma with the anti-tumor-associated-mucin-1 antibody gatipotuzumab: results from a double-blind, placebo-controlled, randomized, phase II study
Jonathan A. Ledermann, Bogdan Żurawski, Francesco Raspagliesi, Ugo De Giorgi, J.Á. Arranz Arija, Mar Marín, Alla Lisyanskaya, Ròbert Póka, Janina Markowska, C. Cebotaru, A. Casado Herráez, Nicoletta Colombo, E. Kutarska, Marcia Hall, Adam Jacobs, I. Ahrens-Fath, Harald Baumeister, Alfredo Zurlo, Jalid Sehouli
Abstract
•Evaluation of the efficacy and safety of a switch maintenance therapy with gatipotuzumab.•Patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer evaluated.•Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced tumor-associated epitope mucin-1.•Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions.•Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients. BackgroundGatipotuzumab 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 methodsIn 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.ResultsOverall, 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.ConclusionsGatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients.Trial registrationClinicalTrials.gov NCT01899599; https://clinicaltrials.gov/ct2/show/NCT01899599 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. 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. 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. Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients.