The purpose of the VicTORia trial was to evaluate efficacy and safety of the combined treatment of everolimus (EVE) and vinorelbine (VIN) compared to VIN monotherapy as second-line treatment for HER2-negative advanced breast cancer. The study was accompanied by an exploratory analysis of phosphoinositide 3 kinase subunit (PIK3CA) as potential predicitve marker for response.
Patients were randomized 1:1 to receive i.v. VIN at a dose of 25 mg/m2 on days 1, 8 and 15 q3w plus 5 mg EVE once daily or i.v. VIN at a dose of 25 mg/m2 on days 1, 8 and 15 q3w. The primary objective was progression-free survival (PFS). Safety and tolerability, overall survival (OS) and overall response rates were secondary objectives. The mutational status of PIK3CA was determined at baseline from plasma samples.The study was initially planned to enroll 166 patients.
Between December 2011 and February 2016 138 patients were enrolled from 32 sites across Germany. Of 69 patients randomized to receive VIN plus EVE, 68 received treatment and 65 of 69 patients randomized to VIN monotherapy received treatment. Baseline characteristics were balanced. Median age was 63 and 62 years, ECOG 0-1 98.5% and 90.7%, postmenopausal status 79.4% and 80.0%, and visceral metastases 89.7% and 87.7%, respectively. Median PFS was 4.01 months [95% CI, 2.40-6.09] for the combination vs. 4.08 months [95% CI, 2.80-5.33] for VIN monotherapy (HR = 1.05 [0.730-1.512], log rank p = 0.7908). The median OS was not statistically different between treatment arms (VIN+EVE: 16.25 months [95% CI, 11.38-18.95] vs. VIN: 13.78 months [95% CI, 10.23-19.05]), log rank p = 0.9361). PIK3CA mutational status was neither associated with PFS nor with OS in the total patient cohort, in patients treated with VIN+EVE and in patients treated with VIN monotherapy, respectively.
The addition of EVE to VIN was not associated with a benefit in PFS. Overall survival also did not significantly differ between treatment arms. No correlation between PIK3CA mutation status and outcome was detected.
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Legal entity responsible for the study
T. Decker: Advisory role or expert testimony: Novartis; Advisory boards, other financial relationships, travel expenses: Novartis. N. Marschner: Advisory role or expert testimony: Novartis; Advisory boards, honoraria: Novartis; Other financial relationships, travel expenses: Novartis. A. Welt: Advisory role or expert testimony: Novartis; Advisory boards, financing of scientific research: Novartis. J. Rauh: Other financial relationships: Honoraria for documentation in clinical studies: Novartis. All other authors have declared no conflicts of interest.