A randomized controlled phase II trial of a novel composition of paclitaxel embedded into neutral and cationic lipids targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC)

EndoTAG-1, composed of paclitaxel embedded in liposomal membranes targeting tumor endothelial cells, was evaluated for safety and efficacy in advanced triple-negative breast cancer (TNBC). One hundred and forty patients were treated with weekly EndoTAG-1 (22 mg/m(2)) plus paclitaxel (70 mg/m(2)), twice weekly EndoTAG-1 (2x 44 mg/m(2)), or weekly paclitaxel (90 mg/m(2)) for greater than or equal to four cycles (3-week treatment + 1-week rest) or until progression/toxicity. Primary end point was progression-free survival (PFS) rate evaluated centrally after four cycles of therapy (week 16). The study was not powered for intergroup comparisons. The PFS rate at week 16 was 59.1% [one-sided 95% CI: 45.6, infinity] on combination treatment, 34.2% [21.6, infinity] on EndoTAG-1, and 48.0% [30.5, infinity] on paclitaxel. Median PFS reached 4.2, 3.4, and 3.7 months, respectively. After complete treatment (week 41 analysis), median overall survival (OS) was 13.0, 11.9, and 13.1 months for the modified Intention-to-Treat (ITT) population and 15.1, 12.5, and 8.9 months for the per-protocol population, respectively. The clinical benefit rate was 53%, 31%, and 36% for the treatment groups. Safety analysis revealed known toxicities of the drugs with slight increases of grade 3/4 neutropenia on combination therapy. Treatment of advanced TNBC with a combination of EndoTAG-1 and standard paclitaxel [Taxol (R) (Bristol-Myers Squibb GmbH), or equivalent generic formulation] was well tolerated and showed antitumor efficacy. The positive trend needs to be confirmed in a randomized phase III trial. European Clinical Trials Database: EudraCT number 2006-002221-23. ClinicalTrials.gov identifier: NCT00448305.