title: A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  NCT01303679.
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon; CNRS UMR5286, Cancer Research Center of Lyon, Lyon.
authors.forename: O
authors.initials: O
authors.lastname: Trédan
authors.affiliation: Department of Medical Oncology, Centre Antoine Lacassagne, Nice.
authors.forename: P
authors.initials: P
authors.lastname: Follana
authors.affiliation: Department of Medical Oncology, Clinique de la Sauvegarde, Lyon.
authors.forename: I
authors.initials: I
authors.lastname: Moullet
authors.affiliation: Direction of Clinical Research and Innovation, Centre Léon Bérard, Lyon.
authors.forename: C
authors.initials: C
authors.lastname: Cropet
authors.affiliation: Department of Medical Oncology, Centre Hospitalier de Senlis, Senlis.
authors.forename: S
authors.initials: S
authors.lastname: Trager-Maury
authors.affiliation: Department of Medical Oncology, Hôpital Mont-De-Marsan, Mont-De-Marsan.
authors.forename: J
authors.initials: J
authors.lastname: Dauba
authors.affiliation: Department of Medical Oncology, CHU Dupuytren, Limoges.
authors.forename: S
authors.initials: S
authors.lastname: Lavau-Denes
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris.
authors.forename: V
authors.initials: V
authors.lastname: Diéras
authors.affiliation: Department of Medical Oncology, Hôpital Privé Jean Mermoz, Lyon.
authors.forename: D
authors.initials: D
authors.lastname: Béal-Ardisson
authors.affiliation: Department of Medical Oncology, Hôpitaux Drôme Nord, Site de Romans, Romans-sur-Isère.
authors.forename: M
authors.initials: M
authors.lastname: Gouttebel
authors.affiliation: Department of Medical Oncology, Hôpital Fleyriat, Bourg-en Bresse.
authors.forename: H
authors.initials: H
authors.lastname: Orfeuvre
authors.affiliation: Department of Medical Oncology, Centre Hospitalier de la Région d'Annecy, Pringy.
authors.forename: L
authors.initials: L
authors.lastname: Stefani
authors.affiliation: Department of Medical Oncology, Institut Jean Godinot, Reims.
authors.forename: C
authors.initials: C
authors.lastname: Jouannaud
authors.affiliation: Department of Medical Oncology, Clinique de l'Union, Saint-Jean.
authors.forename: F
authors.initials: F
authors.lastname: Bürki
authors.affiliation: Department of Medical Oncology, Centre Paul Strauss, Strasbourg.
authors.forename: T
authors.initials: T
authors.lastname: Petit
authors.affiliation: Department of Medical Oncology, Centre Hospitalier la Dracénie, Draguignan.
authors.forename: E
authors.initials: E
authors.lastname: Guardiola
authors.affiliation: Department of Medical Oncology, Oracle, Centre d'Oncologie de Gentilly, Nancy.
authors.forename: C
authors.initials: C
authors.lastname: Becuwe
authors.affiliation: Department of Medical Oncology, Centre Hospitalier Bretagne Atlantique, Vannes.
authors.forename: E
authors.initials: E
authors.lastname: Blot
authors.affiliation: Université Paris Descartes, AP-HP, Hôpitaux Universitaires Paris Centre, Site Hôtel-Dieu, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon; CNRS UMR5286, Cancer Research Center of Lyon, Lyon. Electronic address: thomas.bachelot@lyon.unicancer.fr.
authors.forename: T
authors.initials: T
authors.lastname: Bachelot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D000730:Androstadienes; D000068258:Bevacizumab; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C056516:exemestane
keywords: bevacizumab; endocrine therapy; metastatic breast cancer; taxanes