Trastuzumab-resistant HER2-positive metastatic breast cancer: Comparing results of lapatinib and capecitabine in brain and other metastatic sites.

Abstract

e11505 Background: Trastuzumab, anthracycline, and taxane resistant HER2-positive metastatic breast cancer has poor prognosis. Progression in brain metastasis (BM) commonly leads to difficult diagnostic interpretation and treatment decisions, poor quality of life, and death. Methods: Consented patients (pts) with HER2-positive metastatic breast cancer, ECOG ≤2, with resistance to trastuzumab, taxane, and anthracyclines, were recruited for treatment with daily lapatinib (L) (1,250 mg daily) and capecitabine (C) (2,000 mg/m2/day days 1-14) in a 21 day cycle. Progression was evaluated by RECIST and statistics by SPSS. Results: We enrolled 10 pts (median age 44), median follow up was 19.51 months (M). One patient had grade 3 toxicity due to C and was kept with L only; no other patient discontinued L nor C due to toxicity. Nine (90%) pts had ≥2 metastatic sites, one pt had BM only, and 6 pts had BM in addition to other sites. Median time to progression (TTP) was 9.10 M for the 10 pts, 13.86 M for BM as site of first progression, and 5.90 M for non-BM progression (p<0.05). BM was the most common site for first progression, seen in 4 pts. There was no new BM lesion during treatment. Overall BM response to Tx was 50% (1 complete response, 2 partial responses). In all 4 patients that progressed in central nervous system, head NMR showed enlarged metastatic lesions with central liquefied images, and were interpreted initially as radio/chemo necrosis. Two pts had neurological symptoms and discontinued L and C. The last two pts that progressed in brain had their metastatic images interpreted as necrosis also. However, specific NMR vascular analysis revealed higher perfusion/permeability image patterns, interpreted as caused by tumor activity. They went to BM surgical resection and histology showed tumor cells and 40% of necrosis. Both patients are well and without signs or symptoms after surgery. Conclusions: Brain was the most common metastatic site in this pts, and BM had a longer TTP than the other metastasis. Surgical removal of BM appears to help patients and should be considered in earlier stage of enlargement of lesions. NMR perfusion-permeability studies may facilitate medical decisions. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline