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Clinical Trial
. 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)

Chandra P Belani  1 , Suzanne E Dahlberg  2 , Charles M Rudin  3 , Martin Fleisher  4 , Helen X Chen  5 , Naoko Takebe  5 , Mario R Velasco Jr  6 , William J Tester  7 , Keren Sturtz  8 , Christine L Hann  3 , James C Shanks  9 , Manish Monga  10 , Suresh S Ramalingam  11 , Joan H Schiller  12
Affiliations
Clinical Trial

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)

Chandra P Belani et al. Cancer. .

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.

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Figures

Figure 1
Figure 1
Schema for the E1508 trial. ECOG indicates Eastern Cooperative Oncology Group; PS, performance status; SCLC, small cell lung cancer.
Figure 2
Figure 2
Progression-free survival by treatment.
Figure 3
Figure 3
Overall survival by treatment.
Figure 4
Figure 4
Overall survival by the circulating tumor cell group.
See this image and copyright information in PMC

References

    1. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the Surveillance, Epidemiologic, and End Results database. J Clin Oncol. 2006;24:4539–4544. - PubMed
    1. Chute JP, Chen T, Feigal E, Simon R, Johnson BE. Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol. 1999;17:1794–1801. - PubMed
    1. Peacock CD, Watkins DN. Cancer stem cells and the ontogeny of lung cancer. J Clin Oncol. 2008;26:2883–2889. - PMC - PubMed
    1. Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature. 2003;422:313–317. - PubMed
    1. Rubin LL, de Sauvage FJ. Targeting the hedgehog pathway in cancer. Nat Rev Drug Discov. 2006;5:1026–1033. - PubMed

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