Sylvie Giacchetti1, Anne-Sophie Hamy2, Suzette Delaloge3, Etienne Brain4, Frédérique Berger5, Brigitte Sigal-Zafrani6, Marie-Christine Mathieu7, Philippe Bertheau8, Jean Marc Guinebretière6, Mahasti Saghatchian3, Florence Lerebours4, Chafouny Mazouni9, Olivier Tembo10, Marc Espié11, Fabien Reyal12, Michel Marty13, Bernard Asselain14, Jean-Yves Pierga15. 1. AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, 75475 Paris, France. Electronic address: sylvie.giacchetti@aphp.fr. 2. Institut Curie, PSL Research University, Translational Research Department, INSERM, U932 Immunity and Cancer, Residual Tumor & Response to Treatment Laboratory (RT2Lab), Paris, France. 3. Medical Oncology Department, Gustave Roussy, Cancer Center Villejuif, France. 4. Medical Oncology Department, Institut Curie, Saint Cloud, Paris, France. 5. Biostatistics Department, Institut Curie, Paris, France. 6. Tumor Biology Department, Institut Curie, Saint Cloud, Paris, France. 7. Pathology Department, Gustave Roussy, Cancer Center Villejuif, France. 8. AP-HP, Hôpital Saint-Louis, Pathology Department, University Paris Diderot, Paris, France. 9. Department of Surgery, Gustave Roussy, Cancer Center Villejuif, France. 10. Center for Therapeutic Innovations in Oncology and Haematology (CITOH), APHP, Hôpital Saint-Louis, Paris, France. 11. AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, 75475 Paris, France. 12. Institut Curie, PSL Research University, Translational Research Department, INSERM, U932 Immunity and Cancer, Residual Tumor & Response to Treatment Laboratory (RT2Lab), Paris, France; Department of Surgery, Institut Curie, Paris, France. 13. AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, 75475 Paris, France; Center for Therapeutic Innovations in Oncology and Haematology (CITOH), APHP, Hôpital Saint-Louis, Paris, France. 14. UMR 8081 'IR4M', Université Paris-Sud, 91400 Orsay, France. 15. Medical Oncology Department, Institut Curie, Saint Cloud, Paris, France; Université Paris Descartes, Sorbonne Paris Cite, Paris, France.
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.
RCT Entities:
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.