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/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. Cancer 2016;122:2371-2378. © 2016 American Cancer Society.
authors.affiliation: Penn State Hershey Cancer Institute, Hershey, Pennsylvania.
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.affiliation: ECOG-ACRIN Biostatistics Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Dahlberg
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Martin
authors.initials: M
authors.lastname: Fleisher
authors.affiliation: National Cancer Institute, Rockville, Maryland.
authors.forename: Helen X
authors.initials: HX
authors.lastname: Chen
authors.affiliation: National Cancer Institute, Rockville, Maryland.
authors.forename: Naoko
authors.initials: N
authors.lastname: Takebe
authors.affiliation: Decatur Memorial Hospital, Decatur, Illinois.
authors.forename: Mario R
authors.initials: MR
authors.lastname: Velasco
authors.affiliation: Albert Einstein Cancer Center, Philadelphia, Pennsylvania.
authors.forename: William J
authors.initials: WJ
authors.lastname: Tester
authors.affiliation: Colorado Cancer Research Program, Denver, Colorado.
authors.forename: Keren
authors.initials: K
authors.lastname: Sturtz
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Hann
authors.affiliation: HealthEast Cancer Care, Maplewood, Minnesota.
authors.forename: James C
authors.initials: JC
authors.lastname: Shanks
authors.affiliation: West Virginia University, Morgantown, West Virginia.
authors.forename: Manish
authors.initials: M
authors.lastname: Monga
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D011725:Pyridines / Q000008:administration & dosage; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000813:Anilides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C538724:HhAntag691; D011725:Pyridines; C557414:cixutumumab; D005047:Etoposide; D002945:Cisplatin
keywords: circulating tumor cell (CTC); cixutumumab; extensive disease; small cell lung cancer; vismodegib