ESMO Congress 2023 | OncologyPRO

Abstract 361P

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.