Abstract P2-16-01: Overall Survival Data from SOLTI-0701: A Multinational, Double-Blind, Placebo-Controlled, Randomized Phase 2b Study Evaluating the Oral Combination of Sorafenib and Capecitabine in Patients with Locally Advanced or Metastatic HER2-Negative Breast Cancer

Abstract

Background: Sorafenib (SOR) is an oral multikinase inhibitor with antiangiogenic and antiproliferative activity. We previously reported data from the primary analysis of SOLTI-0701 demonstrating a progressionfree survival (PFS) benefit with the oral regimen of SOR + capecitabine (CAP) vs placebo (PL)+CAP in patients with advanced breast cancer (BC). Here we describe overall survival (OS), a secondary endpoint of SOLTI-0701. Methods: SOLTI-0701 is a multinational (Brazil, France, Spain) phase 2b study in HER2-negative patients with locally advanced or metastatic BC and ≥1 prior chemo regimen for advanced BC. Patients were randomized (1:1) to receive CAP (1000 mg/m2 po, twice daily [BID], 14 of every 21 days) with PL or SOR (400 mg po, BID). The primary endpoint was PFS. The sample size was estimated at 220 patients based on patient accrual projections and the estimated rate of PFS events. OS analysis was planned after 120 events. Results: A total of 229 patients were enrolled (115 SOR+CAP and 114 PL+CAP) from August 2007 to December 2008. Treatment arms were balanced for age (mean 55.2 y), ECOG status 0 (68%) and 1 (30%), stage IV disease (91%), and visceral metastases (75%). In the primary analysis, median PFS was 6.4 mo for the SOR arm vs 4.1 mo for the PL arm (hazard ratio 0.58; 95% CI, 0.41-0.81; 1-sided P=0.0006); the most common Grade 3/4 toxicity was hand-foot skin reaction/syndrome (45% vs 13%, respectively); discontinuation of treatment due to adverse events was infrequent (15% vs 7%, respectively). OS data are expected by the 3rd quarter of this year and will be presented, as well as updated safety data. Conclusions: The oral combination of SOR+CAP significantly improved PFS in patients with advanced BC. The regimen was tolerable with a manageable toxicity profile. An ongoing phase 3 registration trial is evaluating the combination of SOR+CAP for advanced BC. The secondary endpoint of OS will better characterize the potential role of SOR in advanced BC as randomized controlled trials thus far have yet to demonstrate any survival benefit with antiangiogenic agents. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-01.

Targeted therapy in triple-negative metastatic breast cancer: a systematic review and meta-analysis

“…There was no heterogeneity in this analysis ( χ 2 =1.15, df =2; P =0.56; I 2 =0%). One study reported the OS data, and there was no difference between the groups 1,44,45…”

“…One study compared Sor plus CT versus CT in first-line treatment, 37 , 43 and two in second-line treatment. 1 , 36 , 44 , 45 In first-line treatment, Sor (400 mg, orally, twice daily) was associated with paclitaxel, and in second-line treatment Sor was associated with gemcitabine or with capecitabine ( Table 2 ). The response rate was not reported for the TNBC subgroup.…”

Triple negative breast cancer: current status of the problem and unusual case of treatment

“…Однако три рандомизированных двойных слепых плацебо-контролируемых исследования IIb фазы проде-монстрировали улучшенные общие результаты для комбинаций сорафениба с химиотерапией в первой и во второй линиях лечения метаста-тического ТНРМЖ [24,25].…”