SOLTI-0701: A Multinational Double-Blind, Randomized Phase 2b 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).

Abstract

INTRODUCTION: Sorafenib (SOR) is a potent multikinase inhibitor with anti-angiogenic and anti-proliferation activity. It is indicated for the treatment of advanced renal cell carcinoma and unresectable hepatocellular carcinoma. As a single agent, SOR has shown modest activity in patients with advanced BC. Here, we report results from one (SOLTI-0701) of four Phase 2b trials of sorafenib in combination with chemotherapy for advanced breast cancer.METHODS: SOLTI-0701 is a multinational, double-blind, randomized, placebo-controlled phase 2b study in patients with locally advanced or metastatic BC. Eligibility criteria included HER-2 negative tumors and <2 prior chemo regimens for advanced/metastatic BC. Patients with active brain metastasis were excluded. Patients were randomized (1:1) to receive CAP (1000 mg/m2, orally, twice daily [BID], for 14 of every 21 days) with placebo (pl) or SOR (400 mg, orally, BID, continuously). Randomization is stratified by metastatic site (visceral vs nonvisceral). The primary endpoint is progression-free survival (PFS), and secondary endpoints include overall survival, time to progression, response rate, response duration, safety, and QoL. Disease assessments occur every 6 weeks for the first 24 weeks of the study and then every 9 weeks thereafter until disease progression. Based on projected event and accrual rates, a sample size of 220 patients has been calculated. We estimate 120 PFS events within 17 months of study initiation. The study is registered at EudraCT (ID 2007-000290-32).RESULTS: Enrollment began in August 2007 and was completed in December 2008 with 229 patients randomized. Study findings demonstrated that the median PFS was extended in patients treated with SOR and CAP compared to patients receiving CAP and PL. These results were statistically significant (p=0.0006). The safety and tolerability of the combination did not show any new or unexpected toxicities. A subset analysis will be presented.CONCLUSION: The SOLTI-0701 study will provide important efficacy and safety data for the use of sorafenib in combination with oral chemotherapy for advanced breast cancer. These data will help us better understand the potential role for sorafenib in BC and if phase III trials are warranted. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 45.

Targeted therapies for breast cancer

“…Sorafenib is another multikinase inhibitor targeting VEGFR1, VEGFR2, VEGFR3, PDGFRB, RAF, KIT, and FLT-3 (84). In a Phase II randomized trial in breast cancer patients, the addition of sorafenib to capecitabine significantly improved PFS compared with capecitabine alone (PFS 6.4 months versus 4.1 months) (85). The combination of capecitabine plus sorafenib is now being studied (versus capecitabine alone) in a large Phase III study (86).…”

Emerging Trends in the Treatment of Triple-Negative Breast Cancer in Canada: A Survey

“…Similar improvements in PFS among patients with TN disease were seen for the VeGF-inhibitor sorafenib. a subgroup analysis of the SOLTI-0701 trial indicated an improvement in median PFS with the addition of sorafenib to chemotherapy in TNBC (4.2 months vs. 2.5 months, hazard ratio = 0.596) 60 . available prospective randomized data on the use of other targeted agents in TNBC is summarized in Table vi.…”

Triple-Negative Breast Cancer: One Or More Entities?

“…Tyrosine kinase inhibitors targeting the VEGF receptor have also been tested in TNBC in phase II trials. Sunitinib and sorafenib as single agents showed limited activity and significant toxicity when combined with chemotherapy [87][88][89][90]. However, in at least one trial, the combination of sorafenib with capecitabine improved PFS over capecitabine alone (4.3 versus 2.5 months).…”