trial of new multitargeted tyrosine kinase inhibitor
 

for those running out of options and those looking for new hopeful developments--

Abstract 425:
SU11248 (sunitinib malate) therapy in patients with refractory metastatic breast cancer: preliminary safety and efficacy results from a phase II study



Citation: European Journal of Cancer Supplements Volume 4, No. 2, March 2006, page 172

K.D. Miller1, H.J. Burstein2, A.D. Elias3, H.S. Rugo4, M.A. Cobleigh5, A.C. Wolff6, P.D. Eisenberg7, M. Collier8, B.J. Adams8, C.M. Baum8

1Indiana University, Indianapolis, USA
2Dana-Farber Cancer Institute, Boston, USA
3University of Colorado, Health Sciences Center, Denver, USA
4University of California San Francisco, San Francisco, USA
5Rush Presbyterian St. Luke's Medical Center, Chicago, USA
6Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, USA
7California Cancer Care, Inc., Los Angeles, USA
8Pfizer, Inc., La Jolla, USA

Introduction: SU11248 is an oral, multi-targeted tyrosine kinase inhibitor of multiple receptors important in signaling pathways fundamental to tumor growth and survival including PDGFR, VEGFR, KIT, and FLT3. Progression of breast cancer (BC) is dependent on angiogenesis, a process stimulated by autocrine and paracrine signaling involving VEGFR and PDGFR. Results are reported here from a phase II study of SU11248 monotherapy in patients (pts) with previously treated metastatic BC.
Methods: Female pts with unresectable histologically/cytologically confirmed breast adenocarcinoma received oral SU11248 (50 mg/day) for 28 days followed by 14 days off treatment to comprise a 6-week cyclical regimen. Toxicity-related dose reduction was permitted. Response rate was assessed every 2 cycles by RECIST and was the primary endpoint. A total sample size of 63 was required to identify a clinically meaningful ORR ?15% based on Simon's Minimax 2-stage design.
Results: A total of 64 pts (median age 51 years) were enrolled. The majority of pts, 83%, had visceral disease; 61% and 17% were ER+ and HER2+, respectively. Fifty-two pts had received prior adjuvant chemotherapy (anthracycline 90%, taxane 56%) and in the MBC setting 61 pts were previously treated with anthracycline (26%), taxane (69%), capecitabine (66%), vinorelbine (23%), platinum (16%), and gemcitabine (15%). Overall, patients received a median of three prior chemotherapy regimens. The most frequently reported non-hematological grade 2/3 adverse events (AEs) were fatigue (41% and 14%, respectively), diarrhea (20% and 6%, respectively), and nausea (16% and 8%, respectively). Most frequent grade 2/3 hematological AEs were neutropenia (27% and 34%, respectively; no cases of neutropenic fever), anemia (17% and 16%, respectively) and thrombocytopenia (16% and 3%, respectively). One grade 4 AE was reported (neutropenia, which did not result in neutropenic fever). Of the 58 pts who experienced AEs, 24 (38%) required toxicity-related dose-reduction and 34 (53%) required dose interruption. In all, seven pts (11%) achieved a partial response of between 11 and 32 weeks duration. A further three pts (5%) achieved stable disease for ?6 months.
Conclusions: SU11248 has significant single-agent activity and acceptable toxicity in pts with refractory MBC. Toxicity is manageable with dose reductions and/or interruptions. Future studies should include less heavily pre-treated pts and alternative dosing and combination regimens.