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.
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.
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.
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
Legal entity responsible for the study
GEICAM Spanish Breast Cancer Group
Astra Zeneca Astra Zeneca Astra Zeneca Astra Zeneca
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.