Long-term outcome of the REMAGUS 02 trial, a multicenter randomised phase II trial in locally advanced breast cancer patients treated with neoadjuvant chemotherapy with or without celecoxib or trastuzumab according to HER2 status

• Published in: European journal of cancer (1990) 2017-04, Vol.75, p.323-332
• Main Authors: Giacchetti, Sylvie, Hamy, Anne-Sophie, Delaloge, Suzette, Brain, Etienne, Berger, Frédérique, Sigal-Zafrani, Brigitte, Mathieu, Marie-Christine, Bertheau, Philippe, Guinebretière, Jean Marc, Saghatchian, Mahasti, Lerebours, Florence, mazouni, chafouny, Tembo, Olivier, Espié, Marc, Reyal, Fabien, Marty, Michel, Asselain, Bernard, Pierga, Jean-Yves
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Cancer; Celecoxib; Celecoxib - administration & dosage; Chemotherapy; Chemotherapy, Adjuvant; Clinical trials; Cyclophosphamide; Cyclophosphamide - administration & dosage; Epirubicin; Epirubicin - administration & dosage; ErbB-2 protein; Female; Hematology, Oncology and Palliative Medicine; Humans; Immunotherapy; Long-term outcome; Middle Aged; Monoclonal antibodies; Neoadjuvant chemotherapy; Patients; Progesterone; Randomization; Receptor, ErbB-2 - metabolism; Subgroups; Survival; Targeted cancer therapy; Trastuzumab; Trastuzumab - administration & dosage; Treatment Outcome; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2017.01.008

Abstract Background The REMAGUS-02 multicenter randomised phase II trial showed that the addition to neoadjuvant chemotherapy (NAC) of trastuzumab in patients with localised HER2-positive breast cancer (BC) increased the pathological complete response (pCR) rate and that the addition of celecoxib in HER2-negative cases did not increase the pCR rate. We report here the long-term follow-up results for disease-free survival (DFS) and overall survival (OS). Patients and methods From 2004 to 2007, 340 stage II–III BC patients were randomly assigned to receive neoadjuvant EC-T (four cycles of epirubicin–cyclophosphamide followed by four cycles of docetaxel) +/− celecoxib in HER2-negative cases (n = 220) and ± trastuzumab in HER2-positive cases (n = 120). From September 2005, all patients with HER2-positive BC received adjuvant T (n = 106). Results Median follow-up was nearly 8 years (94.4 months, 20–127 m). In the HER2-negative subgroup, addition of celecoxib was not associated with a DFS benefit. Favourable factors were smaller tumour size, expression of progesterone receptor status (PgR) and pCR. In the HER2-positive population, neoadjuvant trastuzumab was not associated with a DFS benefit. Axillary pCR was the only prognostic factor associated with DFS in this group [HR = 0.44, 95% CI = 0.2–0.97], p = 0.035]. To note, DFS and OS were significantly higher in the HER2-positive than in HER2-negative BC patients (HR = 0.58 [0.36–0.92], p = 0.021). Conclusion Celecoxib combined with NAC provided neither pCR nor survival benefit in patients with HER2-negative BC. Absence of PgR is a major prognostic factor. Neoadjuvant trastuzumab increased pCR rates without translation into a DFS or OS benefit compared with adjuvant trastuzumab only. Axillary pCR could be a more relevant surrogate of survival than in the breast in HER2-positive population. A retrospective comparison shows that patients with HER2-positive tumours have a better outcome than HER2-negative BC patients showing the impact of trastuzumab on the natural history of BC.