Background: In recent years, several clinical trials showed that fulvestrant (Ful), alone or in combination with an aromatase inhibitor (AI), is more effective than an AI alone. PACT01 is a randomized neoadjuvant trial of Anastrazole (Ana) alone or in combination with Ful in ER+/HER2- breast cancer.

Methods: Patients with newly diagnosed ER+/HER2- breast cancers, 2 cm or larger in size, were randomized to 16 weeks of Ana (1 mg orally every day) alone or in combination with Ful (500mg IM days 1, 15, 29, and every 28 days thereafter) for 16 weeks. Patients then proceeded to surgery. Tumor tissue was collected at baseline, day 28 (D28), and at the time of surgery. Primary endpoint was the reduction of Ki67 in tumor tissue between baseline and D28. Baseline and D28 samples were stained for ER, PR, HER2, and Ki67. ER and PR were scored for intensity and percentage (H-score), HER2 was scored for intensity of membrane staining; and Ki67 was scored as percentage. Data were summarized descriptively. Changes in biomarkers from baseline to D28 were calculated and compared by Wilcoxon signed rank test.

Results: PACT01 trial enrolled 72 patients. Three of them did not start treatment. Baseline samples were collected from the remaining 69 patients, and D28 samples from 60 patients (5 refused, 2 withdrew, 1 lost to follow up, 1 unknown). Samples from 18 patients had no tumor (5 at baseline, 9 at D28, 4 at both). Of the 42 patients with paired samples, 20 received Ana and 22 received Ana+Ful. All cases except one were centrally confirmed to be ER+, and all were HER2-. Table 1 summarizes median expression of Ki67, ER, and PR. Both treatment regimens led to a significant reduction in Ki67 between baseline and D28. However, Ana+Ful did not reduce Ki67 more effectively than Ana alone. Ki67 was reduced to <10% in 60% of the Ana arm and 68% of the Ana+Ful, which was not statistically significant.PR was similarly reduced in both treatment arms. ER was significantly reduced at D28 in the Ana+Ful arm (p=0.0004) but not in the Ana alone arm. Safety profile of both treatment arms was consistent with package insert and published studies.

Median expression of Ki67, ER and PR in Anastrazole and Anastrazole + Fulvestrant Arms at Baseline and Day 28

ARMTimepointNKi67 (%)ER H-scorePR H-score
Ana Baseline 20 24.8 182.5 100.3 
  Day 28 20 5.6 *170.0 25.0 
Ana + Flu Baseline 22 25.6 198.1 20.5 
  Day 28 22 5.1 *117.5 0.0 
ARMTimepointNKi67 (%)ER H-scorePR H-score
Ana Baseline 20 24.8 182.5 100.3 
  Day 28 20 5.6 *170.0 25.0 
Ana + Flu Baseline 22 25.6 198.1 20.5 
  Day 28 22 5.1 *117.5 0.0 

* p=0.0004. Other comparisons were not stastistically significant

Conclusions:In this small neoadjuvant trial, the addition of Ful to Ana did not increase Ki67 suppression at D28. This may be due to untreated primary tumors being exquisitely sensitive to Ana and that fulvestrant may not add to it. It is also possible that the effect of Ful may be noted later in the course of treatment. Further biomarker data on tissue collected at the end of treatment will be presented at the meeting.

Citation Format: Dhamne S, Nagi C, Wang T, Pavlick AC, Reusser B, Schiff R, Julie N, Niravath P, Silberfein EJ, Sedgwick EL, Sepulveda KA, Gutierrez C, Hilsenbeck SG, Chang JC, Osborne CK, Rimawi MF. Biomarkers of response to neoadjuvant endocrine therapy with anastrozole (Ana) alone or in combination with fulvestrant (Ful) in ER-positive (ER+) HER2-negative (HER2-) breast cancer (PACT01 trial) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-15-05.