1300P - Buparlisib (BKM120) in patients with PI3K pathway-activated, metastatic non-small cell lung cancer (NSCLC): results from the BASALT-1 study

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Jean-Charles Soria
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors J. Soria1, J.F. Vansteenkiste2, J. Canon3, M. Reck4, C. Gridelli5, F. Grossi6, T. De Pas7, J. Gray8, E. Felip9, W. Su10, H. Yoshioka11, G.K. Dy12, M. Thomas13, J. de Greve14, P. Roussou15, G. Atalla-Vidam16, P. Aimone15, S. Thongprasert17
  • 1Institut Gustave Roussy, Institut Gustave Roussy, 94805 - Paris/FR
  • 2Respiratory Oncology Unit (pulmonology), University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE
  • 3Medical Oncology, Grand Hopital de Charleroi, 6000 - Charleroi/BE
  • 4Department Of Thoracic Oncology, Lungen Clinic Grosshandorf, 22927 - Grosshansdorf/DE
  • 5Medical Oncology, Azienda Ospedaliera S. Giuseppe Moscati, 83100 - Avellino/IT
  • 6Lung Cancer Unit, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genoa/IT
  • 7Oncologia, Istituto Europeo di Oncologia, IT-20141 - Milan/IT
  • 8Oncology, Moffitt Cancer Center, 33612 - Tampa/US
  • 9Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 10Oncology, National Cheng Kung University Hospital, Tainan/TW
  • 11Respiratory Medicine Dept., Kurashiki Central Hospital, 710-8602 - Kurashiki/JP
  • 12Medicine, Roswell Park Cancer Institute, 14263 - Buffalo/US
  • 13Int. Oncology Of Thoraxtumor, Thoraxklinik Heidelberg, Heidelberg/DE
  • 14Oncology, UZ Brussel, Laarbeeklaan/BE
  • 15Novartis Ag, Novartis AG, Basel/CH
  • 16Novartis Pharmaceuticals Corporation, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 17Department Of Medicine, Maharaj Nakorn Chiang Mai HospitalFaculty of Medicine, TH-50200 - Chiang Mai/TH

Abstract

Aim

In vitro, NSCLC cell lines with PIK3CA mutations have shown increased sensitivity to the oral pan-PI3K inhibitor buparlisib (BKM120). BASALT-1 is an open-label, two-stage, Phase II study to assess the safety and efficacy of buparlisib in patients (pts) with pre-treated metastatic NSCLC (squamous [sq] and non-squamous [non-sq] histology) and activated PI3K pathway (NCT01297491). Here we report results from the Stage 1 futility analysis (FA) for each histology.

Methods

Pts (≥18 yrs) with previously treated, metastatic NSCLC (sq or non-sq histology) with activated PI3K pathway (defined as PIK3CA mutation and/or PTEN mutation and/or PTEN-negative staining [<10% protein expression at 1+ by IHC] in archival/fresh biopsy) received once-daily, oral buparlisib (100 mg/day). Primary objective: to determine PFS rate at 12 wks in each group. The study will not progress to Stage 2 if the futility criterion (PFS rate <50% at 12 wks) is met.

Results

Thirty pts had been treated in each histologic group at the time of FA (>1200 pts screened). In the sq group, 21 pts were male (median age: 65.5 yrs); in the non-sq group, 19 pts were male (median age: 62.0 yrs). Median treatment exposure was 6.9 (sq group) and 7.2 (non-sq group) wks. Median PFS was 2.79 (95% CI: 1.38, 4.11) and 2.69 (95% CI: 1.41, 2.89) months for the sq and non-sq groups, respectively. PFS rate at 12 wks was 23.3% (95% CI: 9.9, 42.3) for the sq group and 20.0% (95% CI: 7.7, 38.6) for the non-sq group. Best overall responses (RECIST 1.1): partial response (1 pt [3.3%] in each group), stable disease (14 pts [46.7%] in each group), progressive disease (7 pts [23.3%] sq / 9 pts [30.0%] non-sq), unknown (8 pts [26.7%] sq / 6 pts [20.0%] non-sq). Most common (≥30%) AEs possibly related to study drug: hyperglycemia (36.7%), pruritus (33.3%), diarrhea (30%), and nausea (30%) for sq, and asthenia (30%) for non-sq.

Conclusions

In this PI3K pathway-activated group of NSCLC pts, the futility criterion in Stage 1 was met in both histology groups. Thus, enrollment of Stage 2 was not initiated. Results of this study are in line with previous observations where single agents targeting the PI3K pathway have shown marginal activity. Studies of buparlisib in combination with docetaxel in pts with sq NSCLC are ongoing.

Disclosure

J. Soria: - Research funds from Novartis (Instititution) - Compensated advisory board Novartis F. Grossi: Novartis advisory board; E. Felip: Advisory Board: BI, Novartis, Roche, BMS, Lilly; M. Thomas: AD-Board honoraria: Novartis, Roche, Lilly, BMS Speaker honoraria: BMS, Lilly; P. Roussou: - Novartis employee - Shares in Novartis; G. Atalla-Vidam: Novartis employee; P. Aimone: Novartis employee. All other authors have declared no conflicts of interest.