@article{1c0db65d2e2c469c96d2b3425f0cda1d,
title = "Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer: A trial of the ECOG-ACRIN cancer research group (E1508)",
abstract = "BACKGROUND: Preclinical targeting of the hedgehog pathway by vismodegib and of insulin-like growth factor 1 receptor by cixutumumab enhances the efficacy of chemotherapy and also demonstrates activity against the tumor cell fraction responsible for disease recurrence in small cell lung cancer. METHODS: Patients with newly diagnosed extensive-stage small cell lung cancer (SCLC-ED) were randomized to receive four 21-day cycles of cisplatin and etoposide alone (cisplatin at 75 mg/m2 on day 1 and etoposide at 100 mg/ m2 on days 1-3; arm A) or in combination with either vismodegib (150 mg/d by mouth; arm B) or cixutumumab (6 mg/kg/wk intravenously on day 1; arm C). The primary endpoint was progression-free survival (PFS). Circulating tumor cells (CTCs) were isolated/ enumerated with the Veridex CellSearch platform at the baseline. RESULTS: One hundred fifty-two eligible patients were treated. Patient demographics and disease characteristics were well balanced between the 3 arms except for the higher rate with a performance status of 0 in arm B (P 5.03). The median PFS times in arms A, B, and C were 4.4, 4.4, and 4.6 months, respectively; the median overall survival (OS) times were 8.8, 9.8, and 10.1 months, respectively; and the response rates were 48%, 56%, and 50%, respectively. None of the comparisons of these outcomes were statistically significant. The median OS was 10.5 months for those with low CTC counts (_100/7.5 mL) at baseline and 7.2 months for those with high CTC counts (hazard ratio, 1.74; P 5.006). CONCLUSIONS: There was no significant improvement in PFS or OS with the addition of either vismodegib or cixutumumab to chemotherapy in patients with SCLC-ED. A low baseline CTC count was associated with a favorable prognosis.",
keywords = "Circulating tumor cell (CTC), Cixutumumab, Extensive disease, Small cell lung cancer, Vismodegib",
author = "Belani, {Chandra P.} and Dahlberg, {Suzanne E.} and Rudin, {Charles M.} and Martin Fleisher and Chen, {Helen X.} and Naoko Takebe and Velasco, {Mario R.} and Tester, {William J.} and Keren Sturtz and Hann, {Christine L.} and Shanks, {James C.} and Manish Monga and Ramalingam, {Suresh S.} and Schiller, {Joan H.}",
note = "Funding Information: This study was coordinated by the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group (Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, group cochairs) and was supported in part by Public Health Service Grants CA180794, CA180820, CA180802, CA180791, CA189830, CA180790, CA189805, CA189863, CA180844, CA180864, and CA180870 from the National Cancer Institute (National Institutes of Health, Department of Health and Human Services). This article{\textquoteright}s content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. Funding Information: Charles M. Rudin reports acting as a consultant/advisor for Abb-Vie, AVEO, Boehringer Ingelheim, GlaxoSmithKline, Merck, Novartis, Calithera, and Celgene and receiving research funding from Biomarin. Christine L. Hann reports funding from GlaxoS-mithKline. Manish Monga is an employee of and has stock in Bristol-Myers Squibb. Suresh S. Ramalingam reports acting as a consultant for Eli Lilly and Genentech. Joan H. Schiller reports acting as a consultant/advisor for ARIAD, Boehringer Ingelheim, Agennix, Argole Systems, Clovis Oncology, Biodesix, AVEO, Eisai, Genentech/Roche, Synta, Dekkun Corporation, AbbVie, Eli Lilly, and Merck and receiving research funding from Synta, Astex Pharmaceuticals, EMD Serono, Merrimack, Endocyte, Genentech, Novartis, Clovis Oncology, and Johnson and Johnson. Publisher Copyright: {\textcopyright} 2016 American Cancer Society.",
year = "2016",
month = aug,
day = "1",
doi = "10.1002/cncr.30062",
language = "English (US)",
volume = "122",
pages = "2371--2378",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "15",
}