358PD - Vinflunine (VFL) plus capecitabine (CAPE) for advanced breast cancer (ABC) previously treated with or resistant to anthracycline and resistant to t...

Date 28 September 2014
Event ESMO 2014
Session Metastatic and locally advanced breast cancer: Facing with heterogeneity and endpoints in clinical trials
Topics Anticancer Agents
Breast Cancer
Biological Therapy
Presenter Miguel Martin Jimenez
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors M. Martin Jimenez1, Y. Demidchik2, I. Bondarenko3, I. Siedakov4, D. Sakaeva5, S. Krishnamurthy6, L. Roman7, L. Lebedeva8, F. Mefti9, T. Bachelot10, O. Ponomarova11, S. Delaloge12, I. Lytvyn13, A. Kupp14, Y. Karchmit15, P. Bougnoux16, M. Campone17, M.S. Aapro18
  • 1Medical Oncology Service, Hospital General Universitario Gregorio Marañón, 28007 - Madrid/ES
  • 2Oncology, City Clinical Oncology Dispensary, Minsk/BY
  • 3Oncology, Dnipropetrovsk Medical Academy, City Multy-Field Clinical Hospital #4, Dnipropetrovsk/UA
  • 4Oncology, Regional Antitumor Center, Donetsk/UA
  • 5Oncology, Republican Clinical Oncology Dispensary, Ufa/RU
  • 6Oncology, Kidwai Memorial Institute of Oncology, Bangalore/IN
  • 7Oncology, Leningrad Regional Oncology Dispensary, St. Petersburg/RU
  • 8Oncology, Regional Clinical Oncology Dispensary, Arkhangelsk/RU
  • 9Medical Oncology Unit, Hôpital René HUGUENIN, Saint-Cloud/FR
  • 10Oncology, Centre Léon Bérard, 69373 - Lyon/FR
  • 11Oncology, City Oncology Hospital, Kiev/UA
  • 12Breast Cancer Unit, Department Of Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 13Oncology, Regional Oncological Hospital, Dnipropetrovsk/UA
  • 14Oncology, North Estonia Medical Center, Tallinn/EE
  • 15Oncology, Regional Clinical Oncology Dispensary, Vitebsk/BY
  • 16Medical Oncology, CHU Bretonneau, Tours/FR
  • 17Medical Oncology, Centre René Gauducheau, St Herblain/FR
  • 18Oncology, Clinique de Genolier, 1272 - Genolier/CH



VFL a microtubule inhibitor has demonstrated single-agent activity in ABC pretreated with anthracycline (A) and resistant to taxanes (T) and a synergy with CAPE in this setting. This phase 3 study compared VFL plus CAPE with CAPE alone in A-pretreated or -resistant and T-resistant ABC. An update of investigator's assessed PFS and overall survival is presented.


Open-label, multicenter study, with 770 ABC patients with up to 3 prior chemotherapy (CT) regimens randomised to VFL 280 mg/m2 on day 1 plus CAPE 1650 mg/m2 (N = 384) or to CAPE alone at 2500 mg/m2 (N = 386) on days 1 to 14 every 3 weeks. Randomization was stratified by resistance to anthracycline, performance status, disease measurability and number of prior lines of CT for ABC.


Patients had a median age of 54 years (range: 27 - 81); metastatic disease for 97%; anthracycline resistance for 63%; received study treatment as 1st (20%), 2nd (48%) or > 3rd (32%) CT line for ABC. The median number of cycles was 6 for VFL plus CAPE and 5 for CAPE. VFL plus CAPE prolonged PFS assessed by IRC compared to CAPE (median 5.6 vs 4.3 months, HR = 0.84, 95% CI 0.71-0.99, P = 0.0426). This was supported by the investigator assessment (median 5.5 vs 4.1 months, HR = 0.77, 95% CI 0.66-0.90, P = 0.0007). The response rate assessed by IRC was numerically greater for VFL plus CAPE than for CAPE (22.9% vs 17.9%, P = 0.1030); the disease control rate was statistically superior with the combination (57.3% vs 47.9%, P = 0.0089). Median OS analysed after 674 deaths (87.5%) was 13.9 months for VFL plus CAPE and 11.7 months for CAPE (HR = 0.97, 95% CI = 0.83-1.14, P = 0.6976). The most frequent grade 3-4 events were neutropenia for VFL plus CAPE (27.2% of patients vs 6.6% for CAPE) and hand-foot syndrome for CAPE (18% vs 3.7% for VFL plus CAPE). Quality of life global health status score (QLQ-C30) was preserved for VFL plus CAPE while there was a deterioration for CAPE from week 12.


VFL plus CAPE demonstrates a statistically significant improvement in PFS both according to IRC and investigator and a trend towards better OS compared to CAPE alone. VFL plus CAPE is a new well tolerated option for A/T pretreated/resistant patients with ABC.


J. Vedovato: Pierre Fabre employee; M.S. Aapro: Compensated by Pierre Fabre for activity as study chairman. All other authors have declared no conflicts of interest.