Activity and safety of sunitinib in combination with trastuzumab for the treatment of metastatic breast cancer: initial results from a phase II study.

Abstract

Abstract Abstract #4115 Background: Sunitinib (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, FLT3, and CSF-1R, with proven single-agent activity in pts with advanced BC. Trastuzumab (T) is indicated as both monotherapy for second-line treatment and in combination with taxane-based therapies for first-line treatment of metastatic BC. This study investigates the activity and safety/tolerability of SU administered in combination with T in pts with advanced, HER2+ BC.
 Materials and methods: Eligible pts have unresectable, locally recurrent or metastatic HER2+ BC. Pts received SU at a starting dose of 37.5 mg/d po continuous daily dosing (CDD). T was administered iv wkly (loading 4 mg/kg then wkly 2 mg/kg) or q3w (loading 8 mg/kg then 6 mg/kg q3w). Due to changes in standard of care, the trial was amended from a randomized, placebo controlled design, to a single-arm study, and eligibility criteria were changed to allow inclusion of pts who had previously received CT in the first-line setting. Previous treatment with T (± lapatinib) was also permitted. The planned sample size is 53 pts and the primary endpoint is ORR.
 Results: In this ongoing trial, a total of 49 pts have been enrolled to date (6 pts under the original protocol and 43 under the amendment). All 43 pts enrolled under the amendment were evaluable for safety/tolerability, and antitumor activity, measured by RECIST. As of May 2008, 25 pts continue on study and 18 have discontinued, 4 due to AEs. Pts started a total of 167 cycles of treatment with a median of 4 cycles/pt (range: 1–8). The planned dose of SU (37.5 mg/d) was maintained in 31/43 pts (72%). It was reduced to 25 mg/d in 12/43 pts (28%). One pt achieved a CR and 10 a PR. SD occurred in 20 pts and PD in 6 pts. This translated into an ORR of 26% (95% CI, 13.5–41.2) and a clinical benefit rate of 35% (95% CI, 21.0–50.9). Median PFS was 25.3 wks (95% CI, 19.3–32.0). The most common treatment-related AEs were diarrhea (55.8%), asthenia (48.8%) and hypertension (37.2%) of which most were G1 or 2. The most frequent G3 AEs were neutropenia (14%) and asthenia (11.6%). There were 2 treatment-related G4 events: thrombocytopenia (2.3%) and LVEF decline (2.3%). There was 1 treatment-related G5 AE (cardiogenic shock).
 Conclusions: SU 37.5 mg/d on a CDD schedule in combination with T (wkly or q3w) appears to have a manageable safety profile and antitumor activity in pts previously treated for advanced HER2+ BC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4115.