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Cancer. 2016 Aug 1;122(15):2371-8. doi: 10.1002/cncr.30062. Epub 2016 May 10.

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).

Author information

1
Penn State Hershey Cancer Institute, Hershey, Pennsylvania.
2
ECOG-ACRIN Biostatistics Center, Dana-Farber Cancer Institute, Boston, Massachusetts.
3
Johns Hopkins University, Baltimore, Maryland.
4
Memorial Sloan Kettering Cancer Center, New York, New York.
5
National Cancer Institute, Rockville, Maryland.
6
Decatur Memorial Hospital, Decatur, Illinois.
7
Albert Einstein Cancer Center, Philadelphia, Pennsylvania.
8
Colorado Cancer Research Program, Denver, Colorado.
9
HealthEast Cancer Care, Maplewood, Minnesota.
10
West Virginia University, Morgantown, West Virginia.
11
Emory University, Atlanta, Georgia.
12
University of Texas Southwestern Medical Center, Dallas, Texas.

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.

KEYWORDS:

circulating tumor cell (CTC); cixutumumab; extensive disease; small cell lung cancer; vismodegib

PMID:
27163943
PMCID:
PMC4956531
DOI:
10.1002/cncr.30062
[Indexed for MEDLINE]
Free PMC Article

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