@article{129f676887154f9c86c28300fb609a77,
title = "Phase II study of everolimus-erlotinib in previously treated patients with advanced non-small-cell lung cancer",
abstract = "Background: Preclinical data suggest combining a mammalian target of rapamycin inhibitor with erlotinib could provide synergistic antitumor effects in advanced non-small-cell lung cancer (NSCLC). Patients and methods: In this multicenter, open-label, phase II study, patients with advanced NSCLC that progressed after one to two previous chemotherapy regimens were randomized 1:1 to erlotinib 150 mg/day ± everolimus 5 mg/day. Primary end point was the disease control rate (DCR) at 3 months; secondary end points included progression-free survival (PFS) and safety. Results: One hundred thirty-three patients received everolimus-erlotinib (n = 66) or erlotinib alone (n = 67). The DCR at 3 months was 39.4% and 28.4%, respectively. The probability for the difference in disease control at 3 months to be ≥15% was estimated to be 29.8%, which was below the prespecified probability threshold of ≥40%. Median PFS was 2.9 and 2.0 months, respectively. Grade 3/4 adverse events occurred in 72.7% and 32.3% of patients, respectively. Grade 3/4 stomatitis was observed in 31.8% of combination therapy recipients. Conclusions: Everolimus 5 mg/day plus erlotinib 150 mg/day was not considered sufficiently efficacious per the predefined study criteria. The combination does not warrant further investigation based on increased toxicity and the lack of substantial improvement in disease stabilization.",
keywords = "Disease control rate, Erlotinib, Everolimus, Non-small-cell lung cancer, Progression-free survival, Stomatitis",
author = "B. Besse and N. Leighl and J. Bennouna and Papadimitrakopoulou, {V. A.} and N. Blais and Traynor, {A. M.} and Soria, {J. C.} and S. Gogov and N. Miller and V. Jehl and Johnson, {B. E.}",
note = "Funding Information: The authors thank Melanie Leiby, PhD, and Sally Mitchell, PhD (ApotheCom, Yardley, PA, USA), for writing and editorial assistance, which was funded by Novartis Pharmaceuticals Corporation. Funding Information: JB has declared conflicts related to Roche and Boehringer-Ingelheim. NB has received consulting fees from Roche Canada and Novartis Pharmaceuticals (not related to the conduct of this study). AMT is the primary investigator of clinical studies assessing other agents being developed by Novartis Pharmaceuticals, including panobinostat and LDK378. The University of Wisconsin Board of Regents has receiving funding for these clinical trials from Novartis. These studies were not open while the present study of everolimus and erlotinib was active. JCS has served as a consultant to Roche and Novartis Pharma AG. BEJ has received postmarketing royalties from Dana-Farber for EGFR mutation testing, has equity in the KEW Group, a group founded to provide genomic testing guidance for private oncologists, and has served as a consultant to AstraZeneca, Genentech, Sanofi, Millennium, and Transgenomics. SG, NM, and VJ are employees of Novartis Pharma AG. BB has received research grants from Roche and Novartis Pharmaceuticals. VAP has received research grants from Astellas and Novartis Pharmaceuticals. NL declares no conflicts of interest.",
year = "2014",
month = jan,
day = "1",
doi = "10.1093/annonc/mdt536",
language = "English",
volume = "25",
pages = "409--415",
journal = "Annals of Oncology",
issn = "0923-7534",
number = "2",
}