title: Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I-type II study from the GINECO group.
abstract: Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma.
  
  
  
  This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety.
  
  
  
  A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8-6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity.
  
  
  
  The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, 28 Rue Laennec, 69008 Lyon, France.
authors.forename: P-E
authors.initials: PE
authors.lastname: Heudel
authors.affiliation: ICM Val d'Aurelle, Parc Euromédecine 208 Rue des Apothicaires, 34298 Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Fabbro
authors.affiliation: ORACLE Centre d'oncologie de Gentilly, 2 Rue Marie Marvingt, 54100 Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Roemer-Becuwe
authors.affiliation: ICL Institut de Cancérologie de Lorraine, 6 Avenue de Bourgogne Brabois, 54511 Vandoeuvre-les-Nancy, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Kaminsky
authors.affiliation: Institut Sainte Catherine, 250 Chemin de Baigne-pieds, 84918 Avignon, France.
authors.forename: A
authors.initials: A
authors.lastname: Arnaud
authors.affiliation: Centre François Baclesse, Avenue du Général Harris, 14000 Caen, France.
authors.forename: F
authors.initials: F
authors.lastname: Joly
authors.affiliation: Centre Jean Bernard-Clinique Victor Hugo, 18 Rue Victor Hugo, 72000 Le Mans, France.
authors.forename: S
authors.initials: S
authors.lastname: Roche-Forestier
authors.affiliation: Centre hospitalier régional d'Orléans, 14 Avenue de l'Hôpital, 45067 Orléans, France.
authors.forename: J
authors.initials: J
authors.lastname: Meunier
authors.affiliation: Hôpital privé Clairval, 317 Boulevard du Redon, 13009 Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Foa
authors.affiliation: Centre hospitalier Lyon Sud, 165 Chemin du Grand Revoyet, 69495 Pierre-Bénite, France.
authors.forename: B
authors.initials: B
authors.lastname: You
authors.affiliation: Centre hospitalier départemental Les Oudairies, Les Oudairies, 85925 La Roche-sur-Yon, France.
authors.forename: F
authors.initials: F
authors.lastname: Priou
authors.affiliation: Institut de cancérologie Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Tazi
authors.affiliation: Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux, France.
authors.forename: A
authors.initials: A
authors.lastname: Floquet
authors.affiliation: Hôpital Tenon, 4 rue de la Chine 75020 Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Selle
authors.affiliation: ICO centre René Gauducheau, Boulevard Jacques Monod, 44805 Saint Herblain, France.
authors.forename: D
authors.initials: D
authors.lastname: Berton-Rigaud
authors.affiliation: Centre Oscar Lambret, 3 Rue F. Combemale, 59020 Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Lesoin
authors.affiliation: Hôpital Jean Minjoz, 3 Boulevard Alexandre Fleming, 25030 Besançon, France.
authors.forename: E
authors.initials: E
authors.lastname: Kalbacher
authors.affiliation: Centre Catherine de Sienne, 2 Rue Eric Tabarly, 44202 Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Lortholary
authors.affiliation: Centre Georges François Leclerc, 1 Rue Professeur Marion, 21079 Dijon, France.
authors.forename: L
authors.initials: L
authors.lastname: Favier
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, 28 Rue Laennec, 69008 Lyon, France.
authors.forename: I
authors.initials: I
authors.lastname: Treilleux
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, 28 Rue Laennec, 69008 Lyon, France.|UCBL Université Claude Bernard, Lyon I, Lyon, France.
authors.forename: I
authors.initials: I
authors.lastname: Ray-Coquard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000631:Aminopyridines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018269:Carcinoma, Endometrioid / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; D009025:Morpholines; C571178:NVP-BKM120; D000081082:Phosphoinositide-3 Kinase Inhibitors