Fulvestrant Did Not Significantly Improve Response Rate Compared to Anastrozole in ER-Positive, HER2-Negative Early Breast Cancer

According to results from a phase 3 trial, administration of fulvestrant alone or in combination with anastrozole did not significantly improve 6-month endocrine-sensitive disease rate compared to anastrozole alone among postmenopausal patients with estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative, early-stage breast cancer. 

“Adding fulvestrant to anastrozole improved survival in postmenopausal women with advanced ER–positive/[HER2]–negative breast cancer, [however] the combination has not been tested in early-stage disease,” stated Cynthia X. Ma, MD, PhD, Washington University School of Medicine, St Louis, Missouri, and coauthors.

In this trial, 933 postmenopausal patients with stage 2 to 3, ER-positive, HER-negative breast cancer were randomized to receive anastrozole (n = 298), fulvestrant (n = 306), or anastrozole plus fulvestrant (n = 338) for 6 months preoperatively. Tumor ki67 was assessed at week 4 and optionally again at week 12. If tumor ki67 was > 10% at assessment, patients were switched to neoadjuvant chemotherapy or immediate surgery. The primary end point was endocrine-sensitive disease rate, defined as pathologic complete response, or ypT1 to T2N0/N1mic or Ki67 <2.7% residual disease. A key secondary end point was the percentage change in ki67 after 4 weeks of neoadjuvant endocrine therapy. 

At analysis, the endocrine-sensitive disease rate was 18.7% in the anastrozole arm, 22.8% in the fulvestrant arm, and 20.5% in the anastrozole plus fulvestrant arm. The rate of week 4 or week 12 ki67 > 10% was 25.1% in the anastrozole arm, 24.2% in the fulvestrant arm, and 15.7% in the anastrozole plus fulvestrant arm. Following switch to neoadjuvant chemotherapy due to Ki67 >10%, pathologic complete response or residual cancer burden class 1 occurred in 8 of 167 patients and 17 of 167 patients respectively. 

“Neither fulvestrant nor [anastrozole plus fulvestrant] significantly improved the 6-month [endocrine-sensitive disease rate] over anastrozole in ER-rich/ERBB2-negative breast cancer” stated Dr Ma and coauthors. “Aromatase inhibition remains the standard-of-care [neoadjuvant endocrine therapy].” 

Source: 

Ma CX, Suman VJ, Sanati S, et al. Endocrine-sensitive disease rate in postmenopausal patients with estrogen receptor–rich/ERBB2-negative breast cancer receiving neoadjuvant anastrozole, fulvestrant, or their combination. JAMA Oncol. Published online: January 18, 2023. doi:10.1001/jamaoncol.2023.6038