959P - PIK-ORL: A phase II, multicenter trial aiming to evaluate BKM120 in monotherapy in patients (pts) with metastatic/recurrent head and neck squamous...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Head and Neck Cancers
Presenter Jérome Fayette
Citation Annals of Oncology (2016) 27 (6): 328-350. 10.1093/annonc/mdw376
Authors J. Fayette1, L. Digue2, C. Ferlay3, I. Treilleux4, G. Garin3, Q. Wang5, C. Hebert6, C. Even7, D. Cupissol8, S. Couchon-Thaunat9, L. Jaouen10, A. Guyennon9, C. Le Tourneau11, G. Lefebvre12, A. Mailliez12, M. Matias7, M. Degardin12, S. Tartas13, G. Clapisson14, D. Perol10
  • 1Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR
  • 2Department Of Medical Oncology, CHU Bordeaux Hopital St. André, Bordeaux/FR
  • 3Clinical Research, Centre Léon Bérard, Lyon/FR
  • 4Biopathology Department, Centre Léon Bérard, Lyon/FR
  • 5Translational Research Department, Centre Léon Bérard, Lyon/FR
  • 6Medical Oncology, Centre Antoine Lacassagne, Nice/FR
  • 7Medical Oncology, Institut Gustave Roussy, Villejuif/FR
  • 8Medicine, Clinique Val d'Aurelle, Montpellier/FR
  • 9Department Of Radiology, Centre Léon Bérard, Lyon/FR
  • 10Clinical Research, Centre Léon Bérard, 69008 - Lyon/FR
  • 11Dept Of Medical Oncology, Institut Curie, 75005 - Paris/FR
  • 12Medical Oncology, Centre Oscar Lambret, Lille/FR
  • 13Medical Oncology, Hospice Civil de Lyon centre Hospitalier Lyon Sud, Lyon/FR
  • 14Biological Ressouces Center, Centre Léon Bérard, Lyon/FR



The PI3K/AKT pathway activation is an early event in HNSCC and an independent marker of poor outcome that seems to be involved in resistance to cetuximab. BKM120 is an oral, pan-Class I PI3K inhibitor that inhibits tumor growth in HNSCC xenografts.


This Phase II evaluates the clinical benefit of BKM120 (100mg/d, po) in 2 parallel cohorts of HNSCC pts with or without mutation in PI3KCA. Eligible pts progressed after platin and cetuximab or anti-EGFR therapy, and had documented PIK3CA status (exons 9 and 20). The primary endpoint was 2-month Disease Control Rate (DCR2m) as per RECIST 1.1. Secondary endpoints were ORR, PFS, OS, and safety. Blood and tumor samples were obtained for pharmacodynamics (PD). Imaging data were centrally reviewed. Considering that BKM120 would be uninteresting if DCR2m ≤ 10% and promising if ≥ 30% and using Simon's optimal two-stage design (α: 5% unilateral, power: 90%), 7 successes/35 evaluable pts were required for each cohort. Only results of the cohort without PI3KCA mutation are presented. .


36 HNSCC pts without PI3KCA mutation (median age: 58.6 yrs) received at least one dose of BKM120. They were heavily pretreated (33% with at least 3 previous lines). Median treatment duration was 8 wks [min-max: 4 d-55.9 wks]. At the end of 2nd Simon's Stage, the DCR2m was 38.9% (14/36pts). No OR was observed. The most common related AE (>25%) included hyperglycemia, asthenia, anxiety, depression, lymphopenia, anemia, leucocyte increase, hematocrit decrease, nausea and diarrhea. 20 pts (55.6%) presented at least one related AE ≥ Grade 3 (>5%: hyperglycemia, lymphopenia, asthenia, Na or K decrease) and 10 pts (27.8%) prematurely discontinued BKM120 due to an AE. 11pts (30.6%) experienced a related SAE including 3 SUSARs (1 fatal hyperglycemic coma, 1 death of uncertain relationship, 1 severe dehydration). PFS, OS and PD data will be presented at the meeting. Cohort with PI3KCA mutation is ongoing (n = 17).


BKM120 deserves further investigation in relapsing HNSCC pts without PI3KCA mutation, nevertheless with close monitoring of metabolic tolerance.

Clinical trial identification


Legal entity responsible for the study

Centre Leon Bérard


Institut National du Cancer and Fondation ARC


All authors have declared no conflicts of interest.