J Thorac Oncol. 2015 Jun 19. [Epub ahead of print]

Safety and Efficacy of Buparlisib (BKM120) in Patients With PI3K Pathway-Activated Non-Small Cell Lung Cancer (NSCLC): Results From the Phase II BASALT-1 Study.

Vansteenkiste JF1, Canon JL, De Braud F, Grossi F, De Pas T, Gray JE, Su WC, Felip E, Yoshioka H, Gridelli C, Dy GK, Thongprasert S, Reck M, Aimone P,Vidam GA, Roussou P, Wang YA, Di Tomaso E, Soria JC.

Author information

• 11University Hospitals KU Leuven, Leuven, Belgium; 2Grand Hôpital de Charleroi, Charleroi, Belgium; 3Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; 4AOU San Martino IST, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; 5European Institute of Oncology, Milan, Italy; 6Moffitt Cancer Center, Tampa, FL; 7National Cheng Kung University Hospital, Tainan, Taiwan; 8Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; 9Kurashiki Central Hospital, Kurashiki, Japan; 10S.G. Moscati Hospital, Avellino, Italy; 11Roswell Park Cancer Institute, Buffalo, NY; 12Chiang Mai University, Chiang Mai, Thailand; 13LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany; 14Novartis Pharma AG, Basel, Switzerland; 15Novartis Pharmaceuticals Corporation, East Hanover, NJ; 16Novartis Institutes for BioMedical Research, Cambridge, MA; 17Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif, France.

Abstract

INTRODUCTION:

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 pre-screening for PI3K pathway activation, patients with PI3K pathway-activated, metastatic, squamous or non-squamous 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 (PFS) rate for the first 30 patients treated in each group being <50%. Exploratory biomarker analyses were performed in archival tissue samples andcirculating tumor DNA (ctDNA).

RESULTS:

Of 1242 pre-screened patients, 13.5% exhibited PI3K pathway activation. As of June 5, 2014, 63 patients (30 squamous and 33 non-squamous) were treated in Stage 1. The 12-week PFS rates were 23.3% (95% confidence interval [CI] 9.9-42.3) and 20.0% (95% CI 7.7-38.6) in the squamous and non-squamous 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.