E. Gonzalez-Suarez (Barceloma, Spain)
IDIBELL Institut d'investigacio biomedica de BellvitgeAuthor Of 1 Presentation
- A. Vethencourt Casado (Hospitalet de Llobregat, Spain)
- E. Trinidad (Barceloma, Spain)
- C. Gómez Aleza (Barceloma, Spain)
- S. Pernas Simon (Hospitalet de Llobregat, Spain)
- A. Petit (Hospitalet de Llobregat, Spain)
- T. Soler (Hospitalet de Llobregat, Spain)
- A. Urruticoechea (Donostia, Spain)
- A. Gumà Martinez (Hospitalet de Llobregat, Spain)
- A. García-Tejedor (Hospitalet de Llobregat, Spain)
- M. Pla (Hospitalet de Llobregat, Spain)
- C. Capó (Viladecans, Spain)
- M. Gil Gil (Hospitalet de Llobregat, Spain)
- A. Stradella (Hospitalet de Llobregat, Spain)
- A. Fernádez (Hospitalet de Llobregat, Spain)
- S. Recalde (Hospitalet de Llobregat, Spain)
- M. Cejuela (Hospitalet de Llobregat, Spain)
- S. Vazquez (Hospitalet de Llobregat, Spain)
- A. Iserte (Hospitalet de Llobregat, Spain)
- C. Falo (Hospitalet de Llobregat, Spain)
- E. Gonzalez-Suarez (Barceloma, Spain)
14P - Immunomodulatory effect of denosumab in early breast cancer: preliminary results of a randomized window-opportunity clinical trial D-Biomark (NCT03691311).
Abstract
Background
Most breast cancers (BC) exhibit low immune infiltration and are unresponsive to immunotherapy. Hence, the urgency to find new mechanisms of immune activation, postulating receptor activator of nuclear factor kappa-Β ligand (RANKL) and its receptor RANK as potential immunomodulator. Our previous data demonstrated that RANK pathway inhibitors, such as denosumab, used for the treatment of bone metastasis, could also prevent and/or treat BC and regulate the tumour immune crosstalk. However, the population of breast cancer patients who may benefit from denosumab remains to be identified.
Methods
Patients with early-stage HER2-negative BC, candidates to tumour excision as first therapeutic approach are included. Patients are randomized 2:1 to denosumab: control (no treatment); experimental arm received 2 doses of 120 mg subcutaneous denosumab (once per week) before surgery (2-4 weeks later). Putative changes in tumour cell proliferation by Ki67 immunohistochemistry (IHC), cell survival by cleaved caspase 3 IHC (primary endpoints) and stromal tumour infiltrating lymphocytes (TILs) quantified in the haematoxylin and eosin by between baseline (biopsy sample) and surgery are evaluated. Specific antibodies will be used to characterize infiltrating immune populations. Denosumab driven gene expression changes in tumour samples will be analysed and tools such as CIBERSORT will be used to characterize the immune infiltrate.
Results
We present results from the first 36 patients enrolled out of 60. Clinical and tumour characteristics were well balanced between the groups. No relevant toxicities were reported. No clinically significant differences in Ki67 and cleaved caspase-3 were observed after denosumab treatment. Interestingly, a statistically significant increase in TILs was observed in the denosumab treated group (p=0.03, Paired t test) but not in the control group (p=0.80). A 33% of patients treated denosumab showed a ≥10% increase in TILs vs 0% in the control group (p =0.05).
Conclusions
Short term neoadjuvant denosumab increases TILs in early BC.
Clinical trial identification
NCT03691311.
Legal entity responsible for the study
The authors.
Funding
Amgen Juan de la Cierva. Postdoctoral contract. IJCI-2017-31564 Río Hortega (CM19/00148) Instituto de Salud Carlos III / Ministerio de Ciencia, Innovación y Universidades. ERC-Consolidator grant PLEIO-RANK European Research Council.
Disclosure
All authors have declared no conflicts of interest.