Antoine Vasseur1, Luc Cabel1,2, Olivier Tredan3, Marion Chevrier4, Coraline Dubot1, Véronique Lorgis5, William Jacot6, Anthony Goncalves7, Marc Debled8, Christelle Levy9, Jean-Marc Ferrero10, Christelle Jouannaud11, Elisabeth Luporsi12, Marie-Ange Mouret-Reynier13, Florence Dalenc14, Jerome Lemonnier15, Alexia Savignoni4, Marie-Laure Tanguy4, Francois-Clement Bidard1,2, Jean-Yves Pierga16,17. 1. Department of Medical Oncology, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005, Paris & Saint Cloud, France. 2. UVSQ, Paris-Saclay University, Saint Cloud, France. 3. Department of Medical Oncology, Leon Berard Center, Lyon, France. 4. Department of Biostatistics, Institut Curie, PSL Research University, Paris & Saint Cloud, France. 5. Department of Medical Oncology, Georges-François Leclerc Center, Dijon, France. 6. Department of Medical Oncology, Institut du Cancer de Montpellier (ICM) Val d'Aurelle, Montpellier University, IRCM INSERM U1194, Montpellier, France. 7. Aix-Marseille Univ, Inserm U1068, CNRS UMR7258, Institut Paoli-Calmettes, Department of Medical Oncology, CRCM, Marseille, France. 8. Department of Medical Oncology, Institut Bergonie, Bordeaux, France. 9. Department of Medical Oncology, François Baclesse Center, Caen, France. 10. Department of Medical Oncology, Antoine Lacassagne Center, Nice, France. 11. Department of Medical Oncology, Institut Jean Godinot, Reims, France. 12. Department of Medical Oncology, ICL Alexis Vautrin, Vandoeuvre Les Nancy, France. 13. Department of Medical Oncology, Jean Perrin Center, Clermont-Ferrand, France. 14. Department of Medical Oncology, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France. 15. R&D UNICANCER, UCBG, Paris, France. 16. Department of Medical Oncology, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005, Paris & Saint Cloud, France. jean-yves.pierga@curie.fr. 17. Paris Descartes University, Paris, France. jean-yves.pierga@curie.fr.
Abstract
BACKGROUND: Proof of concept studies has reported that circulating endothelial cell (CEC) count may be associated with the outcome of HER2-negative metastatic breast cancer (mBC) patients treated by chemotherapy and the anti-VEGF antibody bevacizumab. We report the results obtained in an independent prospective validation cohort (COMET study, NCT01745757). METHODS: The main baseline criteria were HER2-negative mBC, performance status 0-2 and no prior chemotherapy for metastatic disease. CECs were detected by CellSearch® from 4 ml of blood at baseline and after 4 weeks of weekly paclitaxel and bevacizumab therapy. CEC counts (considered both as a continuous variable and using the previously described 20 CEC/4 ml cutoff) were associated with clinical characteristics and progression-free survival (PFS). RESULTS: CEC count was obtained in 251 patients at baseline and in 207 patients at 4 weeks. Median baseline CEC count was 22 CEC/4 ml (range 0-2231). Baseline CEC counts were associated with performance status (p = 0.02). No statistically significant change in CEC counts was observed between baseline and 4 weeks of therapy. High baseline CEC count was associated with shorter PFS in univariate and multivariate analyses (continuous: p < 0.001; dichotomized: HR 1.52, 95% CI [1.15-2.02], p = 0.004). CEC counts at 4 weeks had no prognostic impact. CONCLUSION: This study confirms that CEC count may be associated with the outcome of mBC patients treated with chemotherapy and bevacizumab. However, discrepancies with previous reports in terms of both the timing of CEC count and the direction of the prognostic impact warrant further clinical investigation.
BACKGROUND: Proof of concept studies has reported that circulating endothelial cell (CEC) count may be associated with the outcome of HER2-negative metastatic breast cancer (mBC) patients treated by chemotherapy and the anti-VEGF antibody bevacizumab. We report the results obtained in an independent prospective validation cohort (COMET study, NCT01745757). METHODS: The main baseline criteria were HER2-negative mBC, performance status 0-2 and no prior chemotherapy for metastatic disease. CECs were detected by CellSearch® from 4 ml of blood at baseline and after 4 weeks of weekly paclitaxel and bevacizumab therapy. CEC counts (considered both as a continuous variable and using the previously described 20 CEC/4 ml cutoff) were associated with clinical characteristics and progression-free survival (PFS). RESULTS: CEC count was obtained in 251 patients at baseline and in 207 patients at 4 weeks. Median baseline CEC count was 22 CEC/4 ml (range 0-2231). Baseline CEC counts were associated with performance status (p = 0.02). No statistically significant change in CEC counts was observed between baseline and 4 weeks of therapy. High baseline CEC count was associated with shorter PFS in univariate and multivariate analyses (continuous: p < 0.001; dichotomized: HR 1.52, 95% CI [1.15-2.02], p = 0.004). CEC counts at 4 weeks had no prognostic impact. CONCLUSION: This study confirms that CEC count may be associated with the outcome of mBC patients treated with chemotherapy and bevacizumab. However, discrepancies with previous reports in terms of both the timing of CEC count and the direction of the prognostic impact warrant further clinical investigation.
Entities:
Keywords:
Bevacizumab; Breast cancer; Circulating endothelial cells
Authors: Mark Jesus M Magbanua; Oleksandr Savenkov; Erik J Asmus; Karla V Ballman; Janet H Scott; John W Park; Maura Dickler; Ann Partridge; Lisa A Carey; Eric P Winer; Hope S Rugo Journal: Clin Cancer Res Date: 2020-06-25 Impact factor: 12.531