A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non-small cell lung cancer.

Autor: Soria JC; Drug Development Department, Institut Gustave Roussy, 114 rue Édouard-Vaillant, 94805 Villejuif Cedex, France; University Paris-Sud University, Orsay, France. Electronic address: jean-charles.soria@gustaveroussy.fr., Adjei AA; Mayo Clinic, 200 1st St. SW, Rochester, MN 55902, USA. Electronic address: adjei.alex@mayo.edu., Bahleda R; Drug Development Department, Institut Gustave Roussy, 114 rue Édouard-Vaillant, 94805 Villejuif Cedex, France. Electronic address: Rastilav.BAHLEDA@igr.fr., Besse B; Department of Medical Oncology, Institut Gustave Roussy, 114 rue Édouard-Vaillant, 94805, Villejuif Cedex, France. Electronic address: Benjamin.BESSE@gustaveroussy.fr., Ferte C; Department of Head and Neck Oncology, Institut Gustave Roussy, 114 rue Édouard-Vaillant, 94805, Villejuif Cedex, France; Drug Development Department, Institut Gustave Roussy, 114 rue Édouard-Vaillant, 94805 Villejuif Cedex, France. Electronic address: Charles.FERTE@gustaveroussy.fr., Planchard D; Department of Cancer Medicine, Institut Gustave Roussy, 114 rue Édouard-Vaillant, 94805, Villejuif Cedex, France. Electronic address: david.planchard@gustaveroussy.fr., Zhou J; Genentech, Inc., South San Francisco, CA, USA. Electronic address: zhou.jing@gene.com., Ware J; Genentech, Inc., South San Francisco, CA, USA. Electronic address: ware.joseph@gene.com., Morrissey K; Genentech, Inc., South San Francisco, CA, USA. Electronic address: morrissey.kari@gene.com., Shankar G; Genentech, Inc., South San Francisco, CA, USA. Electronic address: shankar.geetha@gene.com., Lin W; Genentech, Inc., South San Francisco, CA, USA. Electronic address: lin.wei@gene.com., Schutzman JL; Genentech, Inc., South San Francisco, CA, USA. Electronic address: schutzman.jennifer@gene.com., Dy GK; Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA. Electronic address: grace.dy@roswellpark.org., Groen HJM; Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. Electronic address: h.j.m.groen@umcg.nl.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2017 Nov; Vol. 86, pp. 186-196. Date of Electronic Publication: 2017 Oct 06.
DOI: 10.1016/j.ejca.2017.08.027
Abstrakt: Aim: The phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non-small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC.
Patients and Methods: A 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1-14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, ± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination.
Results: All 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs, serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a '14 days on, 7 days off' schedule. The best confirmed response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%) patients.
Conclusion: Combining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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