A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: Final safety, immunogenicity and survival results.

BACKGROUND: The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. PATIENTS AND METHODS: Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide). Patients then underwent surgery, followed by 10 cycles of adjuvant SB3 or TRZ as randomised. End-points included safety, immunogenicity, event-free survival (EFS) and overall survival through the adjuvant period. RESULTS: Of 875 patients randomised, 764 (SB3, n = 380; TRZ, n = 384) completed the study. The median follow-up duration was 437 days in the SB3 group and 438 days in the TRZ group. The incidence of treatment-emergent adverse events was comparable between groups (SB3, 97.5%; TRZ, 96.1%) during the overall study period. Up to the end of study, the overall incidence of antidrug antibody was low in both treatment groups (3 patients each). EFS was comparable between groups with a hazard ratio (SB3/TRZ) of 0.94 (95% confidence interval, 0.59-1.51) and EFS rates at 12 months of 93.7% for SB3 and 93.4% for TRZ. CONCLUSIONS: Final safety, immunogenicity and survival results of this study further support the biosimilarity established between SB3 and TRZ. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149524); EudraCT (2013-004172-35).

Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer.

BACKGROUND: A phase III randomized trial was activated to evaluate the efficacy of preoperative combined chemotherapy and radiotherapy as compared to preoperative radiation therapy alone, in patients with breast cancer presenting with a clinical stage of IIb-IIIa (TNM classification). PATIENTS AND METHODS: From 1985 to 1990, 271 patients, aged 27-55 years, with stage IIb-IIIa breast cancer were randomized to receive either one or two courses of thiotepa 20 mg (i.m. injection) on the days 1, 3, 5, 7, 9, 11 (total dose per course 120 mg), methotrexate 40 mg/m2, i.v. on days 1 and 8, and 5-fluorouracil 500 mg/m2, i.v. on days 1 and 8 (TMF regimen) plus radiotherapy (Group I, 137 patients), or preoperative radiation therapy only (Group II, 134 patients). After the preoperative treatment all patients underwent mastectomy and complete axillary clearance, and then received 4-6 courses of TMF. The trial was conducted in a single institution (N.N. Petrov Research Institute of Oncology, St. Petersburg). RESULTS: Histopathological assessment of the mastectomy specimens showed complete regression of the tumour in 29.1% of the patients in group I and in 19.4% of the patients e.c. in group II. The estimated 5-year overall survival percentages were 86.1% for group I, and 78.3% for group II (P > 0.05). 5-year disease-free survival percentages were 81.0% and 71.6%, respectively (p < 0.05). CONCLUSIONS: Despite the low number of the patients included in the trial, we were able to detect a significant improvement in treatment results with a combination of chemotherapy and radiation therapy given prior to mastectomy over those of local therapy alone with radiation therapy followed by mastectomy, for average- and high-risk patients with operable breast cancer.