361P - A phase II study of fulvestrant combined with chemotherapy in the neoadjuvant treatment of HR+/HER2- locally advanced breast cancer

Background

HR+/HER2- breast cancer are less sensitive to neoadjuvant chemotherapy (NCT), with a low objective response rate (ORR) of approximately 65% and a much lower pathological complete response (pCR) rate ranging from 5% to 10%. This phase 2 study aims to evaluate the efficacy and safety of adding fulvestrant to NCT in patients (pts) with HR+/HER2- breast cancer, and to investigate the predictive value of ¹⁸F-FES PET/CT for effectiveness.

Methods

In this single-arm phase 2 study, eligible pts were female with histologically confirmed HR+/HER2- locally advanced breast cancer (IIB-IIIC). Pts received fulvestrant (500 mg, on days 0, 14, 28, then every 28 days thereafter, every 4 weeks for six cycles) plus AC-T regimen, followed by surgery. Premenopausal women received a concomitant GnRH analogue. Pts underwent ¹⁸F-FES PET/CT examination at baseline. The primary endpoint was ORR. Secondary endpoints include tpCR (ypT0/is ypN0), overall survival (OS), and safety.

Results

From Dec 2020 to Sep 2022, 36 pts were enrolled. The median age was 53 years (range, 35-67), 78% were ECOG PS 1, 69% were postmenopausal, 92% were nodal involved, and 83% had stage III. After neoadjuvant therapy, the ORR and DCR were 86.1% (95% CI, 70.5%-95.3%) and 100% (95% CI, 90.3%-100.0%), respectively. All pts completed surgery, with a tpCR rate 8.3% (3/36; 95% CI, 1.8%-22.5%). 29 (80.6%; 95% CI, 64.0%-91.8%) pts had pathological tumor response [Miller-Payne (MP) grade ≥3]. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 22% (8/36). The most common TEAEs were neutropenia (13.9%) and leukopenia (8.3%). Among the 36 pts, 24 completed ¹⁸F-FES PET/CT scan at baseline. The average SUV_max in primary breast lesions was 4.17 (range 1.00-12.80). The SUV_max was significantly associated with MP grade (R=0.82, p=8.4e-07). The SUV_max of the primary tumor from pts with MP grade 2/3 was significantly lower than those in pts with MP grade 4/5 (p=2.33e-05).

Conclusions

The addition of fulvestrant to NCT showed manageable toxicity and promising antitumor activity for pts with HR+/HER2- locally advanced breast cancer. The SUV_max of ¹⁸F-FES PET/CT was positively correlated with patient efficacy.

Clinical trial identification

ChiCTR2000041235.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Chia Tai Tianqing Pharmaceutical Group Co., Ltd. L.

Disclosure

All authors have declared no conflicts of interest.