Fulvestrant Falls Short in ER-Rich, HER2- Breast Cancer

Fulvestrant alone or in combination with anastrozole does not provide a benefit over anastrozole alone as neoadjuvant therapy for postmenopausal, estrogen receptor (ER)-rich, HER2-negative, stage II-III breast cancer, according to research published in JAMA Oncology.

In this phase 3 trial, fulvestrant alone or in combination with anastrozole failed to improve the endocrine-sensitive disease rate over anastrozole alone.

The trial (ClinicalTrials.gov Identifier: NCT01953588) included 1298 postmenopausal patients with stage II-III, ER-rich, HER2-negative breast cancer.

The patients were randomly assigned to receive anastrozole alone (n=434), fulvestrant alone (n=430), or anastrozole and fulvestrant (n=434) for 6 months prior to surgery. Patients with a Ki-67 level higher than 10% at week 4 or week 12 were switched to neoadjuvant chemotherapy or immediate surgery.

The study’s primary endpoint was the endocrine-sensitive disease rate, which was defined as the proportion of patients with a pathologic complete response (pCR) or modified preoperative endocrine prognostic index (mPEPI) score of 0.

The endocrine-sensitive disease rate at 6 months was similar across the treatment groups — 18.7% with anastrozole, 22.8% with fulvestrant (P =.98), and 20.5% with the combination (P >.98).

The pCR rate was 1.2% with anastrozole, 0.9% with fulvestrant, and 0.5% with the combination. The proportion of patients with an mPEPI score of 0 was 17.5%, 21.9%, and 20.0%, respectively.

In a multivariate analysis, the likelihood of not achieving endocrine-sensitive disease was greater for patients with cT3-4 disease (adjusted odds ratio [aOR], 2.48; 95% CI, 1.66-3.72; P < .001), cN1-3 disease (aOR, 17.85; 95% CI, 10.05-31.71; P <.001), grade 3 disease (aOR, 1.71; 95% CI, 1.04-2.80; P =.03), or a pretreatment Ki-67 level greater than 20% (aOR, 1.52; 95% CI, 1.10-2.09; P =.01).

A secondary endpoint of this study was the percentage change in Ki-67 level after 4 weeks of neoadjuvant endocrine therapy, which was evaluable in 1122 patients. The median percentage change in Ki-67 level after 4 weeks was -80.6% with anastrozole, -79.1% with fulvestrant (P =.36), and -83.5% with the combination (P =.15).

Ki-67 levels exceeded 10% at week 4 or week 12 in 25.1% of patients treated with anastrozole, 24.2% treated with fulvestrant, and 15.7% treated with the combination. There were 167 patients who switched to neoadjuvant chemotherapy because they had Ki-67 levels greater than 10% at either time point. Of these patients, 4.8% had a pCR, and 10.2% had residual cancer burden class I.

The researchers concluded that this trial did not demonstrate superiority for fulvestrant or the combination of anastrozole and fulvestrant, and “pathologic eradication of disease was uncommon across the arms.”

The researchers added that the limited ER degradation observed with fulvestrant and the combination supports the ongoing development of more effective selective estrogen receptor degraders, and aromatase inhibition remains the standard neoadjuvant endocrine therapy.

Disclosures: This research was partly supported by AstraZeneca and Genentech. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor