Sunitinib as salvage treatment including potent anti-tumor activity in carcinomatous ulcers for patients with multidrug-resistant metastatic breast cancer.

Bing Sun,Xin Zhao,Shikai Wu,Lijuan Ding,Xiangying Meng,Santai Song

doi:10.18632/oncotarget.11082

Abstract

ObjectiveTo evaluate the efficacy and safety of single-agent sunitinib as salvage treatment in Chinese patients with multidrug-resistant metastatic breast cancer (MBC).Results37 patients were enrolled with median age of 48 years. 17 had hormone receptor (HR)-positive tumors, 7 had HER2-positive tumors, and 10 had triple-negative tumors. Among 32 evaluable patients with follow-up, 6 (18.8%) achieved partial response, 14 (43.8%) achieved stable disease, and 11 (34.4%) exhibited tumor shrinkage. The response rate in 9 patients with carcinomatous ulcers was 77.8%. The median progression free survival (PFS) was 8.6 weeks. Patients with a better response had improved overall survival and PFS relative to patients with a worse response (p = 0.007, p < 0.001). Compared with HR-negative tumor, HR-positive tumor had significantly better response to sunitinib (p = 0.035). The most frequent non-hematologic adverse events were fatigue (82.8%) and hypertension (34.5%). Grade 3/4 hematologic toxicity included neutropenia (82.8%) and thrombocytopenia (79.3%). There was no correlation between the clinical response and IHC findings.Materials and MethodsPatients with MBC who were resistant to multiple salvage regimens (≥ 3 previous chemotherapy lines) were enrolled to receive sunitinib monotherapy. Dosage adjustment was allowed depending on adverse events. 14 patients underwent immunohistochemistry (IHC) testing for VEGF, PDGFR, EGFR and c-KIT.ConclusionsSunitinib salvage treatment provided modest antitumor effect to patients with refractory multidrug-resistant MBC, especially to those with troublesome carcinomatous ulcers. The treatment-related adverse events of sunitinib were manageable through dosage adjustment.

Highlights

Medical treatment is the major treatment option for patients with metastatic breast cancer (MBC)
Several studies confirmed that PDGF signaling pathway implicated in the pathogenesis of breast cancer, and angiogenesis was inhibited in breast cancer www.impactjournals.com/oncotarget xenografts by sunitinib [5, 6]
Thirty-seven Chinese MBC patients were enrolled with median age of 48 years

Summary

Results

Thirty-seven Chinese MBC patients were enrolled with median age of 48 years (range 27–70). Among the 3 patients achieved PR, there was a 45-year-old woman with ER (+), PR (+) and HER2 (−) disease showed resistance to endocrine therapy, taxanes and anthracyclines She was treated with sunitinib on a dosage of 37.5 mg/day in the eighth-line setting. The first 10 patients received 50 mg/day all experienced grade III/IV toxicity of neutrophil or platelet with median treatment time of 2 weeks. They had to reduce the dosage to 37.5 mg/day schedule. For the target dose of 37.5 mg/day, a total of 14 (37.8%) patients experienced dosage reduction, and 12 (32.4%) patients required interruption of sunitinib due to adverse events. Other common adverse events included rash, cerebral hemorrhage and nausea

Materials and Methods

Conclusions

Introduction

Discussion

Acknowledgments and Funding

Conflicts of Interest