Tocilizumab Therapy for TNBC

Triple-negative breast cancer (TNBC) carries a relatively poorer prognosis than other subtypes of breast cancer. Since there is no targeted therapy specifically recommended for TNBC, the treatment for these patients is surgery and chemotherapy/immunotherapy. Therefore, there is an urgent need to identify new targets to improve treatment outcomes in TNBC patients and to solve the paucity in treatment options.

TNBC and active cancer-associated fibroblast (CAFs) secrete the highest levels of IL-6, which is involved in mediating resistance to chemotherapeutic regimens and supports tumor progression by activating different signaling pathways. Targeting the IL-6 pathway could pave the way toward the development of novel and efficient therapeutic options for this very aggressive breast cancer subtype.

We aim to inhibit IL-6 in TNBC cells and active CAFs using the FDA-approved anti-IL-6 receptor Tocilizumab (Actemra), both in vitro and in vivo. We aim to determine the tolerability, safety, and toxicity profiles, and to determine the complete pathological response rate, both in breast and axilla, as a surrogate for improved disease-free and overall survival, as well as the efficacy of combining tocilizumab with cisplatin/docetaxel in locally advanced triple-negative breast cancer patients. Thirty (30) patients with (T2-T4, N0-3) stage (IIB-III) TNBC were included in this phase I/II trial. They had a median age of 42 years, 63% were premenopausal, and 67% had nodal involvement at baseline. The median tumor size was 45 mm (range 25-150 mm), stage III A/B 26% and stage IIIC 50%. Germline BRCA1/2 mutations represented 27% of the patients. The overall pCR (RCB class 0) and (RCB class 0+1) were 62% and 65%, and pCR in axilla was reached by 81% of patients. Interestingly, patients with BRCA1/2 mutated tumors achieved 100% pCR rate, and 70% of patients with tumor-infiltrating lymphocytes (TILs) of >30% achieved pCR.

This clinical trial shows, for the first time, that the sequential administration of tocilizumab followed by cisplatin/docetaxel is a highly efficient neoadjuvant treatment for locally advanced TNBC patients, which generated unprecedented responses, especially in patients with tumors bearing BRCA1/2 mutations. SCTR 19111002 (Saudi Food and Drug Authority).