O Trédan1, P Follana2, I Moullet3, C Cropet4, S Trager-Maury5, J Dauba6, S Lavau-Denes7, V Diéras8, D Béal-Ardisson9, M Gouttebel10, H Orfeuvre11, L Stefani12, C Jouannaud13, F Bürki14, T Petit15, E Guardiola16, C Becuwe17, E Blot18, E Pujade-Lauraine19, T Bachelot20. 1. Department of Medical Oncology, Centre Léon Bérard, Lyon; CNRS UMR5286, Cancer Research Center of Lyon, Lyon. 2. Department of Medical Oncology, Centre Antoine Lacassagne, Nice. 3. Department of Medical Oncology, Clinique de la Sauvegarde, Lyon. 4. Direction of Clinical Research and Innovation, Centre Léon Bérard, Lyon. 5. Department of Medical Oncology, Centre Hospitalier de Senlis, Senlis. 6. Department of Medical Oncology, Hôpital Mont-De-Marsan, Mont-De-Marsan. 7. Department of Medical Oncology, CHU Dupuytren, Limoges. 8. Department of Medical Oncology, Institut Curie, Paris. 9. Department of Medical Oncology, Hôpital Privé Jean Mermoz, Lyon. 10. Department of Medical Oncology, Hôpitaux Drôme Nord, Site de Romans, Romans-sur-Isère. 11. Department of Medical Oncology, Hôpital Fleyriat, Bourg-en Bresse. 12. Department of Medical Oncology, Centre Hospitalier de la Région d'Annecy, Pringy. 13. Department of Medical Oncology, Institut Jean Godinot, Reims. 14. Department of Medical Oncology, Clinique de l'Union, Saint-Jean. 15. Department of Medical Oncology, Centre Paul Strauss, Strasbourg. 16. Department of Medical Oncology, Centre Hospitalier la Dracénie, Draguignan. 17. Department of Medical Oncology, Oracle, Centre d'Oncologie de Gentilly, Nancy. 18. Department of Medical Oncology, Centre Hospitalier Bretagne Atlantique, Vannes. 19. Université Paris Descartes, AP-HP, Hôpitaux Universitaires Paris Centre, Site Hôtel-Dieu, Paris, France. 20. Department of Medical Oncology, Centre Léon Bérard, Lyon; CNRS UMR5286, Cancer Research Center of Lyon, Lyon. Electronic address: thomas.bachelot@lyon.unicancer.fr.
Abstract
BACKGROUND: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS: In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks oftaxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV: NCT01303679.
RCT Entities:
BACKGROUND: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS: In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBCpatients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV: NCT01303679.
Authors: Eva Ciruelos; José Manuel Pérez-García; Joaquín Gavilá; Analía Rodríguez; Juan de la Haba-Rodriguez Journal: Clin Drug Investig Date: 2019-07 Impact factor: 2.859
Authors: Michael Yamakawa; Susan J Doh; Samuel M Santosa; Mario Montana; Ellen C Qin; Hyunjoon Kong; Kyu-Yeon Han; Charles Yu; Mark I Rosenblatt; Andrius Kazlauskas; Jin-Hong Chang; Dimitri T Azar Journal: Med Res Rev Date: 2018-03-12 Impact factor: 12.944
Authors: Anouk K M Claessens; Reinier Timman; Jan J Busschbach; Jeanette M Bouma; Jeany M Rademaker-Lakhai; Frans L G Erdkamp; Vivianne C G Tjan-Heijnen; Monique E M M Bos Journal: Breast Cancer Res Treat Date: 2019-11-28 Impact factor: 4.872