LBA8 - A phase III randomized, double-blind, trial comparing sorafenib plus capecitabine versus placebo plus capecitabine in the treatment of locally adva...

Date 28 September 2014
Event ESMO 2014
Session Breast cancer, metastatic
Topics Anticancer Agents
Breast Cancer
Biological Therapy
Presenter José Baselga
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors J. Baselga1, C. Zamagni2, P. Gomez3, B. Bermejo4, S. Nagai5, B. Melichar6, A. Chan7, L. Mangel8, J. Bergh9, F.P. Costa10, H.L. Gomez11, W. Gradishar12, C. Hudis13, B. Rapoport14, H. Roche15, P. Maeda16, L. Huang17, J. Zhang16, L.S. Schwartzberg18
  • 1Hematology Oncology, Memorial Sloan-Kettering Cancer Center, 10128 - New York/US
  • 2Breast & Gynaecological Medical Oncology Unit, S. Orsola-Malpighi Hospital, 40138 - Bologna/IT
  • 3Breast Cancer Unit, Vall d’Hebron University Hospital, 08035 - Barcelona/ES
  • 4Breast Cancer Group, Hospital Clinico Universitario de Valencia, Valencia/ES
  • 5Department Of Breast Oncology, Saitama Cancer Center, 3620806 - Saitama/JP
  • 6Oncology, University Hospital Olomouc Palacky University, Faculty of Medicine, 77520 - Olomouc/CZ
  • 7Breast Clinical Trials Unit, Mount Hospital, Breast Cancer Research Centre - WA and Curtin University, 6000 - Perth/AU
  • 8N/a, Pecsi Tudomanyegyetem OEKK, Pecs/HU
  • 9Oncology-radimnemmet, Karolinska Institutet & University Hospital, SE-171 76 - Stockholm/SE
  • 10Oncologia Clínica, Hospital Sírio Libanes, 01308-000 - Sao Paulo/BR
  • 11Medical Oncology, Instituto Nacional de Enfermedades Neoplasicas, 34 - Lima/PE
  • 12Dept. Medicine, Hemato/oncology, Northwestern University FeinbergSchool of Medicine, 60611 - Chicago/US
  • 13Dept Of Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 14Medical Oncology, The Medical Oncology Centre of Rosebank, Johannesburg/ZA
  • 15Oncology Dept, Institut Claudius-Regaud, 31052 - Toulouse CEDEX/FR
  • 16Global Clinical Development, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 17Gl Clinical Statistics, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 18Hematology & Oncology, The West Clinic, Memphis/US




A phase III randomized, double-blinded, placebo (PLC)-controlled study of sorafenib (S) in combination with capecitabine (C) was conducted in patients with HER2-negative, locally advanced or metastatic breast cancer. The primary endpoint was progression-free survival (PFS) per independent review. Secondary endpoints included overall survival (OS), time to progression (TTP), objective response rate (ORR), disease control rate (DCR) and safety.


Patients resistant to prior taxane and resistant to prior anthracycline or for whom further anthracycline was not indicated, and having received no more than one prior regimen for advanced disease were randomized 1:1 to PLC or S (600 mg daily, po, 21-day schedule) in combination with C (1000 mg/m2, bid, po, 14/7 days on/off).


A total of 537 patients were randomized: 266 to S + C and 271 to PLC + C. The two arms were generally well balanced; median age 54 years; 69% hormone receptor positive and 31% triple negative; and 43%/57% having received 0/1 prior lines of chemotherapy for metastatic disease. Median PFS was 5.5 mo for S + C and 5.4 mo for PLC + C; HR 0.973 (95% CI: 0.779, 1.217; one-sided p-value = 0.406). Median OS was 18.9 mo for S + C and 20.3 mo for PLC + C; HR 1.195 (95% CI: 0.943, 1.513; one-sided p-value = 0.930). There were no differences in TTP, ORR or DCR. The incidence of grade 3 AEs was 58.5% vs 39.3%, grade 4 AEs 5.8% vs 4.5%, and grade 5 AEs 6.2% vs 4.5%, S + C vs PLC + C arms, respectively. The most commonly reported grade 3 AEs included palmar-plantar erythrodysesthesia syndrome (16% vs 8%), hypertension (14% vs 2%), fatigue (7% vs 3%) diarrhea (4% vs 6%), neutropenia (4% vs 5%), and anemia (5% vs 2%). The average daily dose for C was 1734 mg/m2 vs 1914 mg/m2 with a median duration of 18 wks vs 23 wks for C in S + C and PLC + C arms, respectively. There was one drug-related grade 5 AE (hepatic failure) reported in the S + C arm.


S + C did not improve PFS compared to PLC + C for patients with HER2-negative, locally advanced or metastatic breast cancer. The types of AEs observed were consistent with the known safety profiles of S and C. There was a trend toward worse OS in the S + C arm that is not readily explained by study treatment-related toxicity.


P. Gomez: Honoraria: Bayer; B. Melichar: Honoraria: Bayer, Roche; J. Bergh: Clinical research: Bayer, Amgen, Astra-Zeneca, Merck, Pfizer, Roche and Sanofi-Aventis; P. Maeda, L. Huang and J. Zhang: Employment: Bayer HealthCare Pharmaceuticals. All other authors have declared no conflicts of interest.