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


CONCLUSIONS
Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC.
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. russell.schilder@jefferson.edu
Russell J
RJ
Schilder
William E
WE
Brady
Heather A
HA
Lankes
James V
JV
Fiorica
Mark S
MS
Shahin
Xun C
XC
Zhou
Robert S
RS
Mannel
Harsh B
HB
Pathak
Wei
W
Hu
R Katherine
RK
Alpaugh
Anil K
AK
Sood
Andrew K
AK
Godwin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077216:Carcinoma, Ovarian Epithelial; D000069439:Dasatinib; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*
C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib