title: Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study.
abstract: BACKGROUND
  The phosphatidylinositol 3-kinase (PI3K) pathway promotes tumor growth and treatment resistance in non-small cell lung cancer (NSCLC). The aim of the open-label, two-stage, Phase II study BASALT-1 (NCT01820325) was to investigate the pan-PI3K inhibitor buparlisib (BKM120) in patients with PI3K pathway-activated, relapsed NSCLC.
  
  
  METHODS
  After prescreening for PI3K pathway activation, patients with PI3K pathway-activated, metastatic, squamous or nonsquamous NSCLC, who had relapsed after prior systemic antineoplastic therapy, were enrolled. In Stage 1, patients received single-agent buparlisib (100 mg/day). A futility analysis was performed independently in each histology group, based on the 12-week progression-free survival rate for the first 30 patients treated in each group being less than 50%. Exploratory biomarker analyses were performed in archival tissue samples and circulating tumor DNA (ctDNA).
  
  
  RESULTS
  Of 1242 prescreened patients, 13.5% exhibited PI3K pathway activation. As of June 5, 2014, 63 patients (30 squamous and 33 nonsquamous) were treated in Stage 1. The 12-week progression-free survival rates were 23.3% (95% confidence interval: 9.9-42.3) and 20.0% (95% confidence interval: 7.7-38.6) in the squamous and nonsquamous groups, respectively. Stage 2 was therefore not initiated in either group. PI3K pathway mutations in ctDNA were more concordant with metastatic tissue than with primary biopsies.
  
  
  CONCLUSIONS
  Despite preselecting patients for targeted treatment, BASALT-1 did not meet its primary objective during Stage 1. PI3K pathway activation can be detected using ctDNA, but may not be the main oncogenic driver in NSCLC. Combinations of PI3K inhibitors with other agents may demonstrate greater efficacy than monotherapy.
authors.affiliation: University Hospitals KU Leuven, Leuven, Belgium. Electronic address: johan.vansteenkiste@uzleuven.be.
authors.forename: Johan F
authors.initials: JF
authors.lastname: Vansteenkiste
authors.affiliation: Grand Hôpital de Charleroi, Charleroi, Belgium.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Canon
authors.affiliation: Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: De Braud
authors.affiliation: AOU San Martino IST, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Grossi
authors.affiliation: European Institute of Oncology, Milan, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: De Pas
authors.affiliation: Moffitt Cancer Center, Tampa, Florida.
authors.forename: Jhanelle E
authors.initials: JE
authors.lastname: Gray
authors.affiliation: National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
authors.affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.affiliation: Kurashiki Central Hospital, Kurashiki, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.affiliation: S.G. Moscati Hospital, Avellino, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
authors.affiliation: Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Dy
authors.affiliation: Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Sumitra
authors.initials: S
authors.lastname: Thongprasert
authors.affiliation: LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Aimone
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Gena Atalla
authors.initials: GA
authors.lastname: Vidam
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Pantelia
authors.initials: P
authors.lastname: Roussou
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
authors.forename: Ying A
authors.initials: YA
authors.lastname: Wang
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Di Tomaso
authors.affiliation: Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000368:Aged; D000631:Aminopyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*
chemical_list: D000631:Aminopyridines; D009025:Morpholines; C571178:NVP-BKM120; D019869:Phosphatidylinositol 3-Kinases