拉帕替尼可与foretinib安全联用于HER2+乳腺癌

foretinib即XL880，靶点包括C-MET 、VEGFR2、PDGFRB、AXL、FLT3、TIE-2、RET、RON。联合拉帕替尼有助延迟拉帕耐药，具体数据有待公布，联合是安全的，但需要减量,foretinib不超过45mg，拉帕不超过1000mg每天。

草根抗癌可以用2992+XL184模拟，当然也要减量。


Background: The mechanisms of resistance to targeted anti-HER 2 therapy are unclear. Proposed pathway
include MET, VEGF and AXL. Multi-targeted pathway inhibition may delay or prevent acquired resistanc
to HER2 inhibition. Foretinib, an oral multi-kinase inhibitor of MET and VEGFR2, as well as PDGFRB、AXL, FLT3, TIE-2, RET and RON kinases, has pre-clinical anti-tumor activity in breast tumor models. Th phase 1b study sought to establish the associated toxicities, pharmacokinetics (PK) and recommended phas II doses (RP2D) of this combination of oral tyrosine kinases inhibitors in a cohort of HER-2 positive MB patients.

Methods: Women with HER2 positive (determined locally) MBC, PS 0-2, and no limit on numbe of prior chemotherapies or lines of anti-HER2 therapies were enrolled. A 313 dose escalation design wautilized. 4 dose levels were planned with starting doses of foretinib 30 mg and lapatinib 750 mg PO OD (dose level 1) on a q 4 weekly cycle. Correlative studies from primary archival tissue are planned. Results 19 patients were enrolled, all of whom were evaluable for toxicity assessment and 16 were evaluable for response. Median age was 60 years (34-86), 95% were PS 0-1, 53% were ER- and 95% had at least one prio anti-HER2 based regimen. A median of 2 cycles (range: 1-20) was delivered across 4 dose levels. At th 4th dose level (foretinib 45 mg/lapatinib 1250 mg) dose limiting toxicities were documented in 4/7 patient These included grade 3 fatigue (2 cases); grade 3 ALT elevation; grade 3 diarrhea and grade 2 joint effusion There was only one grade 4 non-hematological toxicity (grade 4 vomiting: dose level 1) across all dos levels. One patient discontinued treatment due to toxicity with grade 3 limb edema and grade 3 proteinuri PK of both drugs from DL1-3 did not appear to demonstrate a significant interaction. The RP2D was
declared to be foretinib 45 mg and lapatinib 1000 mg PO OD. The full efficacy data and correlative studie will be presented at the meeting.

Conclusions: The combination of foretinib and lapatinib can safely by delivered together, though at lower doses than either agent alone.

哪里可以买到相对便宜些的拉帕替尼？