Sunitinib alone or in combination with chemotherapy for the treatment of advanced breast cancer: A systematic review and meta-analysis

Article type: Research Article

Authors: Elgebaly, Ahmed^{a; b} | Menshawy, Ahmed^{a; b} | El Ashal, Gehad^{a; c} | Osama, Omnya^{a; c} | Ghanem, Esraa^{a; b} | Omar, Ahmed^{a; c} | Negida, Ahmed^{a; d; e; f; *}

Affiliations: [a] Medical Research Group of Egypt, Egypt | [b] Faculty of Medicine, Al Azhar University, Cairo, Egypt | [c] Kasr Al ainy School of Medicine, Cairo University, Cairo, Egypt | [d] Faculty of Medicine, Zagazig University, Zagazig, El-Sharkia, Egypt | [e] Student Research Unit, Zagazig University, Zagazig, El-Sharkia, Egypt | [f] CURE and MORE national research collaborative

Correspondence: [*] Corresponding author: Ahmed Negida, Medical Research Group of Egypt, Faculty of Medicine, Zagazig University, and Student Research Unit, Zagazig, El-Sharkia, Postal code 44519, Egypt. Tel.: +20 1125549087; E-mail: [email protected]

Abstract: INTRODUCTION:Sunitinib is an orally delivered tyrosine kinase inhibitor that exhibits antiangiogenic effects. FDA has approved sunitinib for the treatment of metastatic renal cell carcinoma. However, its efficacy for the treatment of advanced breast cancer (ABC) remains controversial. Therefore, we performed this systematic review and meta-analysis to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of sunitinib alone and in combination with chemotherapy for the treatment of ABC. METHODS:We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search of PubMed, SCOPUS, web of knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL) has been conducted using relevant keywords. Studies were screened for eligibility and data were extracted to an online data extraction form. Progression free survival (PFS) and overall survival (OS) were pooled as Hazard ratio (HR) in a meta-analysis model using generic inverse variance method. Objective response rate (ORR) and complications were pooled as relative risk (RR) in a random effect model meta-analysis using Mantel–Haenzel method. RESULTS:Six RCTs, with a total sample size of 2273 patients, met our eligibility criteria and were included in this meta-analysis. Sunitinib monotherapy was not superior to chemotherapy in terms of PFS (HR = 1.00, 95% CI [0.86 to 1.16], P = 0.99), OS (HR = 1.07; 95% CI [0.87 to 1.32], P = 0.5), or ORR (RR = 0.70, 95% CI [0.74 to 1.03], P = 0.07). Sunitinib in combination with chemotherapy did not show superiority to chemotherapy in terms of PFS (HR = 0.99, 95% CI [0.86 to 1.14], P = 0.89) and OS (HR = 1.04, 95% CI [0.85 to 1.28], P = 0.69). However, the ORR favored sunitinib in combination with chemotherapy group (RR = 1.15, 95% CI [1.01 to 1.31]) with a statistically significant P value (P = 0.03). CONCLUSIONS:Current evidence shows that sunitinib, either alone or in combination with chemotherapy, has no clinical benefit for patients with advanced breast cancer. However, previous studies did not considered patient stratification and outcome assessment based on molecular markers. In terms of safety, toxicity was common with sunitinib treatment.

Keywords: Breast, cancer, sunitinib, tyrosine kinase inhibitor, vascular endothelium growth factor, metastasis, chemotherapy

DOI: 10.3233/BD-160218

Journal: Breast Disease, vol. 36, no. 2-3, pp. 91-101, 2016