Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: A Gynecologic Oncology Group study

Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: A Gynecologic Oncology Group study

Publication year: 2012
Source:Gynecologic Oncology, Volume 127, Issue 1
Russell J. Schilder, William E. Brady, Heather A. Lankes, James V. Fiorica, Mark S. Shahin, Xun C. Zhou, Robert S. Mannel, Harsh B. Pathak, Wei Hu, R. Katherine Alpaugh, Anil K. Sood, Andrew K. Godwin
Objectives Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome. Methods Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment. Primary endpoints were progression-free survival (PFS) ≥6months and response rate. Serial plasma samples were assayed for multiple biomarkers. Circulating free DNA was quantified as were circulating tumor and endothelial cells. Results Thirty-five (35) patients were enrolled in a two-stage sequential design. Of the 34 eligible and evaluable patients, 20.6% (90% confidence interval: 10.1%, 35.2%) had a PFS ≥6months; there were no objective responses. Grade 3–4 toxicities were gastrointestinal (mostly nausea and emesis; n =4), pulmonary (dyspnea and/or pleural effusion; n =4) and pain (n =5), and infrequent instances of anemia, malaise, insomnia, rash, and central nervous system hemorrhage. Lack of clinical activity limited any correlation of biomarkers with outcome. Conclusion Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC.

Highlights

► No objective responses with 7 of 34 patients had PFS ≥6months. ► The agent was well tolerated with the major toxicities being grade 3 nausea/emesis, pain and pulmonary. ► No detectable relationships between clinical outcome and biomarkers.

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