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)

• Type of Material: Article
• Authors: Chandra P. Belani, Penn State Hershey Cancer Institute; Suzanne E. Dahlberg, Dana Farber Cancer Institute; Charles M. Rudin, Johns Hopkins University; Martin Fleisher, Memorial Sloan Kettering Cancer Center; Helen X. Chen, National Cancer Institute; Naoko Takebe, National Cancer Institute; Mario R. Velasco, Decatur Memorial Hospital; William J. Tester, Albert Einstein Cancer Center; Keren Sturtz, Colorado Cancer Research Program; Christine L. Hann, Johns Hopkins University; James C. Shanks, HealthEast Cancer Care; Manish Monga, West Virginia University; Suresh Ramalingam, Emory University; Joan H. Schiller, University of Texas Southwestern Medical Center
• Language: English
• Date: 2016-05-10
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 American Cancer Society.
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.30062
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 122
• Issue: 15
• Start Page: 2371
• End Page: 2378
• Grant/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).
• Keywords: Life Sciences & Biomedicine; circulating tumor cell (CTC); HEDGEHOG PATHWAY; EFFICACY; Oncology; GROWTH; extensive disease; INHIBITION; cixutumumab; SAFETY; small cell lung cancer; Science & Technology; vismodegib
• Research Categories: Health Sciences, General

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/m 2 on day 1 and etoposide at 100 mg/m 2 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 = .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 = .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.