148O - Phase III evaluating the addition of fulvestrant (F) to Anastrozol (A) as adjuvant therapy in postmenopausal women with hormone receptor positive H...

Date 08 September 2017
Event ESMO 2017 Congress
Session Breast cancer, early stage
Topics Anticancer agents
Breast Cancer
Prostate Cancer
Therapy
Biological therapy
Presenter Manuel Ruíz-Borrego
Citation Annals of Oncology (2017) 28 (suppl_5): v43-v67. 10.1093/annonc/mdx362
Authors M. Ruíz-Borrego1, M. Martin Jimenez2, A. Ruiz3, A. Lluch4, M. Ramos5, J. Cruz Jurado6, J.M. Baena-Canada7, B. Cirauqui8, A. Rodriguez-Lescure9, E. Alba Conejo10, N. Martínez Jañez11, M. Muñoz12, S. Antolin13, I. Álvarez López14, S. Del Barco15, L. Garcia-Estevez16, J..I. Chacon Lopez-Muniz17, A. Anton Torres18, E. Carrasco19
  • 1Oncologia, Hospital Virgen del Rocío, - - Sevilla/ES
  • 2Medical Oncology, Hospital General Universitario Gregorio Marañon, GEICAM, CIBERONC., 28009 - Madrid/ES
  • 3Clinical Oncology, Instituto Valenciano de Oncología, Valencia/ES
  • 4Medical Oncology  , Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 5Medical Oncology, Centro Oncologico de Galicia, A Coruña/ES
  • 6Clinical Oncology, Hospital Universitario de Canarias, 38320 - San Cristobal de la Laguna/ES
  • 7Clincal Oncology, H. U. Puerta del Mar, 11009 - Cadiz/ES
  • 8Clincal Oncology, Institut Català d’Oncologia Badalona, Hospital Universitario Germans Trias i Pujol, Badalona/ES
  • 9Medical Oncology, H G U de Elche, Elche Alicante/ES
  • 10Clinical Oncology, Hospital Universitario Virgen de la Victoria, GEICAM, CIBERONC, 29010 - Malaga/ES
  • 11Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid/ES
  • 12Clinical Oncology, 12H Clinic i Provincial de Barcelona, Barcelona/ES
  • 13Clinical Oncology, 13Complejo Hospitalario U A Coruña, Coruña/ES
  • 14Medical Oncology, Hospital Universitario Donostia, 20014 - Donostia/ES
  • 15Clinical Oncology, 15Instituto Catalan de Oncologia de Girona, Girona/ES
  • 16Medical Oncology, Centro Integral Oncologico Clara Campal, Madrid/ES
  • 17Clinical Oncology, Hospital Virgen de la Salud, 49004 - Toledo/ES
  • 18Clinical Oncology, Hospital Miguel Servet, 50009 - Zaragoza/ES
  • 19Scientific Director, GEICAM, Madrid/ES

Abstract

Background

F is a selective estrogen receptor degrader for HR+ advanced breast cancer patients (pts). We designed this trial to compare A vs. A in combination with F (A+F) to address the hypothesis that a complete estrogen blockade can prevent resistance to aromatase inhibitors in the adjuvant setting.

Methods

This was a multicenter, open label, phase III study in which HR+/HER2- EBC postmenopausal pts were randomized 1:1 to A for 5 years (y) or A+F (A concurrently with F 250mg/4 weeks for 3y followed by 2y of A). Pts were stratified for prior chemotherapy (yes/no); number of positive lymph-nodes (0/1-3/≥4); HR status (both positive/one positive) and site. Primary objective was disease-free survival (DFS). To detect an absolute 5-y DFS increase of 3% (90% A, 93% A+F) a sample size of 2716 evaluable patients was required. On 2010, when the negative results of the FACT trial were made available, the financer decided to stop the study support after the inclusion of 872 pts.

Results

From January 2008 to June 2010, 437 pts were randomized to A and 435 to A+F. Pts characteristics were well balanced between arms; median age was 62 y (40-86), 46.9% were N0, 89.5% ER+/PgR+ and 68.2% had received prior chemotherapy. Treatment was completed as planned by 72.5% and 48.5% of A and A+F pts. Median relative dose intensity was 99% for A (both arms) and 81% for F. Most relevant G2-3 toxicities (>5% in either arm) with A vs. A+F were hypertension (13.2%; 9.9%), fatigue (5.2%; 11.8%), LDL-Cholesterol increase (9.4%; 5.3%), osteoporosis (5.5%; 6.9%) and musculoskeletal bone/joint pain (26.3%; 29.4%). After a median follow-up of 6.3y, the proportion of pts disease free at 5y was 90.99% (A 90.77%, A+F 91.25%, D = 0.48%, p = 0.357); 9.4% had BC relapse (A 10.5%; A+F 8.3%, D = 2.2%) and 4.3% had secondary tumors (A 3.9%; A+F 4.6%). Survival and breast cancer-specific survival were not reached.

Conclusions

The GEICAM/2006-10 study failed to demonstrate a statistically significant increase in DFS adding F to A as adjuvant therapy, though no formal conclusion can be extracted from this trial due to the F administered dose and the actual trial sample size.

Clinical trial identification

NCT00543127

Legal entity responsible for the study

GEICAM Spanish Breast Cancer Group

Funding

Astra Zeneca Astra Zeneca Astra Zeneca Astra Zeneca

Disclosure

M. Martin Jimenez: Speaker honoraria and AstraZeneca advisory boards participation. J.M. Baena-Canada: Consulting/relationship advice for AstraZeneca. M. Muñoz: Advisory Board from AstraZeneca. All other authors have declared no conflicts of interest.