330P - Randomized phase II study of neoadjuvant chemotherapy with denosumab compared to chemotherapy alone in hormonal receptor-positive, HER2-negative premenopausal breast cancer patients

Background

High RANK mRNA levels were linked with several adverse prognostic factors in breast cancer. The present study aims to assess the activity of neoadjuvant chemotherapy combined with denosumab compared to chemotherapy alone in premenopausal patients with hormonal receptors (HR) positive, HER2 negative breast cancer.

Methods

In this single centre randomized phase II study, we enrolled patients with ER Allred score 4-8 at diagnostic biopsy with either locally advanced inoperable tumours or tumours that need downsizing to allow for breast conservative surgery (BCS). Enrolled patients were randomised between neoadjuvant chemotherapy (4 cycles of epirubicin/doxorubicin with cyclophosphamide and 4 cycles of docetaxel) and denosumab vs. the same chemotherapy alone. Patients in the experimental arm received subcutaneous denosumab 120 mg starting with 1^st chemotherapy cycle and then with every other cycle (total of 4 doses). Residual cancer burden (RCB) was the primary endpoint.

Results

We recruited 50 patients (26 in control arm, 24 in experimental arm). Different baseline characteristics were balanced between the 2 arms including age at diagnosis, ER Allred score (≤6 vs. >6), PR status, Ki67 level, clinical-T, clinical N stage, and clinical stage (stage II vs. III). Noteworthy, 86% of patients were node-positive, 44% had cT4 tumours and 80% had ER Allred score >6. Two patients in the control arm did not undergo breast surgery (1 lost follow up, 1 had local progression). No difference in the rate of BCS (58.3% in both arms). No difference in RCB between control and experimental arms (RCB 0-1: 25% vs 20.8%, respectively, p=0.73). Similarly, no difference in pathological T-stage (pT0-1: 87.5% vs 70.8%, p=0.29), pathological N-stage (N0: 41.7% vs 29.2%, p=0.55) or pathological stage (41.6% vs 33.3%, p=0.75). No significant difference in adverse events profiles between the two arms.

Conclusions

Adding denosumab to neoadjuvant chemotherapy was not associated with lower RCB or improved pathological stage in premenopausal HR+/HER2-negative breast cancer patients with comparable rate of BCS. No new safety signal with the addition of denosumab.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

King Abdullah Medical City, Saudi Arabia.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.