Phase II study of SU11248, a multitargeted receptor tyrosine kinase inhibitor (TKI), in patients (pts) with previously treated metastatic breast cancer (MBC)

Abstract

563 Background: Autocrine and paracrine signaling involving VEGFR and PDGFR are implicated in angiogenesis and proliferation of BC. SU11248, an oral multitargeted TKI with both antiangiogenic and anittumor activity, inhibits VEGF, PDGF, KIT, and FLT3 receptor TKs. Therefore, SU11248 was studied in pts with previously treated MBC. Methods: Eligible pts had histologically confirmed MBC and had received prior chemotherapy regimens that must have included treatment with an anthracycline and taxane; measurable disease was required. Pts were treated with SU11248, 50 mg daily, in repeating 6-wk cycles of 4 wks of dosing followed by 2 wks without treatment. The primary endpoint was ORR defined by RECIST. Sample size was calculated using Simon’s Minimax 2-stage design to identify a clinically meaningful ORR ≥15%. The first stage will enroll 38 pts, with a second cohort of 25 to be enrolled if >2/38 pts achieve confirmed PRs. Results: The study has enrolled 37/38 pts in the first stage. Preliminary data are available on a subset of pts. Median age is 52.5 years (range 38–70) in the 24 pts with available data. Pts had received a median of 3.5 prior chemotherapy regimens (range 2–5). 65% of pts were ER and/or PgR+; 20% were HER2+. Detailed toxicity data are available for 22 pts. The most frequently reported SU11248-related adverse events of any grade include diarrhea (32%), nausea (27%), fatigue (23%), hypertension (14%), headache (9%) and rash (5%). Laboratory data available for 37 patients showed grade 3 events of neutropenia (6 pts), thrombocytopenia (2 pts), and AST increase (1 pt), with one grade 4 event of ALT increase. No treatment-related SAEs have been reported to date. Patients were evaluated for response after every 2 cycles of therapy. Preliminary efficacy data are available for 23 pts. PR = 4 (17%, two of which have been confirmed), SD = 5, PD = 14. The remaining patients are too early for response assessment. Conclusion: SU11248 is well tolerated in pts with previously treated MBC. The objective responses observed are encouraging and support proceeding to the second stage of accrual. Update efficacy results will be available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer