A phase II study of combined VEGF inhibitor (bevacizumab+sorafenib) in patients with metastatic breast cancer: Hoosier Oncology Group Study BRE06-109
Lida A Mina, Menggang Yu, Cynthia Johnson, Cyndi Burkhardt, Kathy D Miller, Robin Zon, Lida A Mina, Menggang Yu, Cynthia Johnson, Cyndi Burkhardt, Kathy D Miller, Robin Zon
Abstract
Purpose: Angiogenesis plays an essential role in tumor development, invasion and metastasis. We evaluated the efficacy and safety of dual angiogenesis blockade with bevacizumab and sorafenib in patients with metastatic breast cancer.
Patients and methods: Patients who had received no more than 2 prior chemotherapy regimens in any setting were treated with sorafenib 200 mg as a single oral dose daily plus bevacizumab intravenously 5 mg/kg every other week. Response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST). The primary endpoint was progression free survival (PFS).
Results: Eighteen patients were enrolled. Median age was 56 yo, all had good performance status KPS of 0 or 1, and 17 patients had received 1 or 2 prior chemotherapy regimens. Median PFS was 2.8 months. There were no complete or partial responses; 3 patients had stable disease for >6 months. Toxicity was substantial with 9 (50 %) patients reporting Grade 3 toxicity. Seven (39 %) patients discontinued therapy due to adverse events including hypertension (N=2), GI toxicity (N=1), sensory neuropathy (N=1), rash (N=1), pain (N=1) and wound complication (N=1). Given the lack of clear efficacy and increased toxicity, accrual was terminated.
Conclusion: The combination of sorafenib and bevacizumab has substantial toxicity and minimal efficacy in patients with previously treated metastatic breast cancer. Further study of this combination is not recommended.
References
- Greenberg PA, et al. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol. 1996;14:2197–2205. doi: 10.1200/JCO.1996.14.8.2197.
- Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997;18:4–25. doi: 10.1210/edrv.18.1.0287.
- Bhardwaj B, et al. Localization of platelet-derived growth factor beta receptor expression in the periepithelial stroma of human breast carcinoma. Clin Cancer Res. 1996;2:773–782.
- Coltrera MD, Wang J, Porter PL, Gown AM. Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor beta subunit in human breast tissue and breast carcinoma. Cancer Res. 1995;55:2703–2708.
- Huang J, Li X, Hilf R, Bambara RA, Muyan M. Molecular basis of therapeutic strategies for breast cancer. Curr Drug Targets Immune Endocr Metabol Disord. 2005;5:379–396. doi: 10.2174/156800805774912944.
- Moreno-Aspita A, Hillman D, Wisenfeld TJ, et al (2006) BAY 43–9006 as single oral agent in patients with metastatic breast cancer previously exposed to anthracycline and/or taxane. ASCO abstract 577
- Baselga J, Gianni L, Gradishar WJ et al (2009) Phase IIb double-blind, randomized, placebo-controlled trials for the efficacy and safety of sorafenib in patients (pts) with metastatic or locally advanced breast cancer (BC): review of the Trials to Investigate the Effects of Sorafenib in BC (TIES) program. Presented at: 2009 ASCO Annual Meeting. Chicago, IL, USA, 4–8 June 2009
- Gradishar WJ, Kaklamani V, Prasad Sahoo T, et al (2009) A double- blind, randomized, placebo-controlled, phase 2b study evaluating the efficacy and safety of sorafenib (SOR) in combination with paclitaxel (PAC) as a first-line therapy in patients (pts) with locally recurrent or metastatic breast cancer (BC). Presented at: 32nd Annual San Antonio Breast Cancer Symposium. December 10–13, 2009. Abstract 44
- Baselga J, Grupo Español de Estudio Tratamiento y Otras Estrategias Experimentales en Tumores Sólidos, Roché H et al (2009) SOLTI-0701: A multinational double-blind, randomized Phase IIB study evaluating the efficacy and safety of sorafenib compared to placebo when administered in combination with capecitabine in patients with locally advanced or metastatic breast cancer (BC). Presented at: ECCO 15 and 34th ESMO Multidisciplinary Congress. Berlin, Germany, 20–24 September (2009) (Abstract 3LBA). Updated at: 32nd Annual San Antonio Breast Cancer Symposium. San Antonio, TX, USA, 9–13 December 2009 (Abstract 45). Demonstrates significant activity of sorafenib in combination with capecitabine
- Azad NS, et al. Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol. 2008;26:3709–3714. doi: 10.1200/JCO.2007.10.8332.
- Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–481. doi: 10.1080/01621459.1958.10501452.
- Sosman J, Flaherty K, Atkins M, et al. Updated results of phase I trial of sorafenib (S) and bevacizumab (B) in patients with metastatic renal cell cancer (mRCC) J Clin Oncol. 2008;26(15S):A5011. doi: 10.1200/jco.2008.26.15_suppl.5011.
- Feldman DR, et al. Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27:1432–1439. doi: 10.1200/JCO.2008.19.0108.
- Mayer EL, et al. SABRE-B: an evaluation of paclitaxel and bevacizumab with or without sunitinib as first-line treatment of metastatic breast cancer. Ann Oncol. 2010;21:2370–2376. doi: 10.1093/annonc/mdq260.
- Rini BI, et al. A phase I study of sunitinib plus bevacizumab in advanced solid tumors. Clin Cancer Res. 2009;15:6277–6283. doi: 10.1158/1078-0432.CCR-09-0717.
- Socinski MA, Scappaticci FA, Samant M, Kolb MM, Kozloff MF. Safety and efficacy of combining sunitinib with bevacizumab+paclitaxel/carboplatin in non-small cell lung cancer. J Thorac Oncol. 2010;5:354–360. doi: 10.1097/JTO.0b013e3181c7307e.
Source: PubMed