Safety and preliminary efficacy of adding tocilizumab to cisplatin/docetaxel for the treatment of locally advanced triple-negative breast cancer patients: prospective phase 1/2 clinical trial

Triple-negative breast cancer (TNBC) remains a challenge for clinicians due to its aggressive behavior and scarcity of effective treatment. Interleukin 6 (IL-6) is well known to contribute to poor therapeutic gain, tumor relapse, and aggressive tumor growth. Here, we have explored targeting the IL-6 signaling pathway by tocilizumab (Actemra) as a new potential therapeutic approach for the treatment of TNBC patients. The participants were treated uniformly with tocilizumab on day 1, followed by cisplatin/docetaxel on day 2 every 4 weeks for a total of six cycles according to a traditional 3 + 3 design using a sentinel patient in each cohort. The primary objective of the safety run-in was tolerability/toxicity profiles, while the secondary endpoints included efficacy and pathological complete response (pCR) in breast and axilla (ypT0/ypN0). The status of the BRCA1 and BRCA2 genes was determined by DNA sequencing in all 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. All assessable patients (n = 28) underwent surgery after neoadjuvant therapy (tocilizumab plus chemotherapy). The overall pCR (RCB class 0) was 62%, and pCR in the axilla was reached by 81% of the treated patients. Patients with tumors bearing mutated BRCA1/2 achieved a 100% pCR rate. The present clinical trial shows that tocilizumab-dependent inhibition of the IL-6 signaling in a sequential fashion with chemotherapy is safe and tolerable for neoadjuvant treatment of the intricate and hard-to-treat TNBC patients.Trial registration: ISRCTN50182475 “Safety and effectiveness of tocilizumab followed by cisplatin/docetaxel in advanced triplenegative breast cancer” (retrospective registration 19/03/2025). https://doi.org/10.1186/ISRCTN50182475 . SCTR 19,111,002 (Saudi Food and Drug Authority) “Singlearm Phase I/II study of the safety, tolerability and efficacy of the Tocilizumab followed by cisplatin/docetaxel in patients with triple negative locally advanced breast cancer” (registration date 12/03/2020).