PMID- 28072765 OWN - NLM STAT- MEDLINE DCOM- 20170608 LR - 20191210 IS - 1532-1827 (Electronic) IS - 0007-0920 (Print) IS - 0007-0920 (Linking) VI - 116 IP - 3 DP - 2017 Jan TI - 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. PG - 303-309 LID - 10.1038/bjc.2016.430 [doi] AB - 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. FAU - Heudel, P-E AU - Heudel PE AD - Department of Medical Oncology, Centre Leon Berard, Centre de Recherche en Cancerologie de Lyon, 28 Rue Laennec, 69008 Lyon, France. FAU - Fabbro, M AU - Fabbro M AD - ICM Val d'Aurelle, Parc Euromedecine 208 Rue des Apothicaires, 34298 Montpellier, France. FAU - Roemer-Becuwe, C AU - Roemer-Becuwe C AD - ORACLE Centre d'oncologie de Gentilly, 2 Rue Marie Marvingt, 54100 Nancy, France. FAU - Kaminsky, M C AU - Kaminsky MC AD - ICL Institut de Cancerologie de Lorraine, 6 Avenue de Bourgogne Brabois, 54511 Vandoeuvre-les-Nancy, France. FAU - Arnaud, A AU - Arnaud A AD - Institut Sainte Catherine, 250 Chemin de Baigne-pieds, 84918 Avignon, France. FAU - Joly, F AU - Joly F AD - Centre Francois Baclesse, Avenue du General Harris, 14000 Caen, France. FAU - Roche-Forestier, S AU - Roche-Forestier S AD - Centre Jean Bernard-Clinique Victor Hugo, 18 Rue Victor Hugo, 72000 Le Mans, France. FAU - Meunier, J AU - Meunier J AD - Centre hospitalier regional d'Orleans, 14 Avenue de l'Hopital, 45067 Orleans, France. FAU - Foa, C AU - Foa C AD - Hopital prive Clairval, 317 Boulevard du Redon, 13009 Marseille, France. FAU - You, B AU - You B AD - Centre hospitalier Lyon Sud, 165 Chemin du Grand Revoyet, 69495 Pierre-Benite, France. FAU - Priou, F AU - Priou F AD - Centre hospitalier departemental Les Oudairies, Les Oudairies, 85925 La Roche-sur-Yon, France. FAU - Tazi, Y AU - Tazi Y AD - Institut de cancerologie Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France. FAU - Floquet, A AU - Floquet A AD - Institut Bergonie, 229 Cours de l'Argonne, 33076 Bordeaux, France. FAU - Selle, F AU - Selle F AD - Hopital Tenon, 4 rue de la Chine 75020 Paris, France. FAU - Berton-Rigaud, D AU - Berton-Rigaud D AD - ICO centre Rene Gauducheau, Boulevard Jacques Monod, 44805 Saint Herblain, France. FAU - Lesoin, A AU - Lesoin A AD - Centre Oscar Lambret, 3 Rue F. Combemale, 59020 Lille, France. FAU - Kalbacher, E AU - Kalbacher E AD - Hopital Jean Minjoz, 3 Boulevard Alexandre Fleming, 25030 Besancon, France. FAU - Lortholary, A AU - Lortholary A AD - Centre Catherine de Sienne, 2 Rue Eric Tabarly, 44202 Nantes, France. FAU - Favier, L AU - Favier L AD - Centre Georges Francois Leclerc, 1 Rue Professeur Marion, 21079 Dijon, France. FAU - Treilleux, I AU - Treilleux I AD - Department of Medical Oncology, Centre Leon Berard, Centre de Recherche en Cancerologie de Lyon, 28 Rue Laennec, 69008 Lyon, France. FAU - Ray-Coquard, I AU - Ray-Coquard I AD - Department of Medical Oncology, Centre Leon Berard, Centre de Recherche en Cancerologie de Lyon, 28 Rue Laennec, 69008 Lyon, France. AD - UCBL Universite Claude Bernard, Lyon I, Lyon, France. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20170110 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (Aminopyridines) RN - 0 (Antineoplastic Agents) RN - 0 (Morpholines) RN - 0 (NVP-BKM120) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) SB - IM MH - Aged MH - Aged, 80 and over MH - Aminopyridines/*therapeutic use MH - Antineoplastic Agents/*therapeutic use MH - Carcinoma, Endometrioid/*drug therapy/pathology MH - Chemotherapy, Adjuvant MH - Disease Progression MH - Endometrial Neoplasms/*drug therapy/pathology MH - Female MH - Humans MH - Middle Aged MH - Morpholines/*therapeutic use MH - Neoplasm Recurrence, Local/pathology MH - Phosphoinositide-3 Kinase Inhibitors MH - Recurrence MH - Treatment Outcome PMC - PMC5294485 COIS- The authors declare no conflict of interest except F Joly who declares NOVARTIS board expert. EDAT- 2017/01/11 06:00 MHDA- 2017/06/09 06:00 PMCR- 2018/01/31 CRDT- 2017/01/11 06:00 PHST- 2016/06/13 00:00 [received] PHST- 2016/11/14 00:00 [revised] PHST- 2016/12/04 00:00 [accepted] PHST- 2017/01/11 06:00 [pubmed] PHST- 2017/06/09 06:00 [medline] PHST- 2017/01/11 06:00 [entrez] PHST- 2018/01/31 00:00 [pmc-release] AID - bjc2016430 [pii] AID - 10.1038/bjc.2016.430 [doi] PST - ppublish SO - Br J Cancer. 2017 Jan;116(3):303-309. doi: 10.1038/bjc.2016.430. Epub 2017 Jan 10.