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, Suzanne E. Dahlberg, Charles M. Rudin, Martin Fleisher, Helen X. Chen, Naoko Takebe, Mario R. Velasco, William J. Tester, Keren Sturtz, Christine Hann, James C. Shanks, Manish Monga, Suresh S. Ramalingam, Joan H. Schiller

Research output: Contribution to journalArticle

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 = .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.

Original languageEnglish (US)
JournalCancer
DOIs
StateAccepted/In press - 2016

Fingerprint

HhAntag691
Small Cell Lung Carcinoma
Circulating Neoplastic Cells
Arm
Drug Therapy
Research
Disease-Free Survival
Neoplasms
Cell Count
Etoposide
Cisplatin
Survival
Somatomedin Receptors
Mouth
anti-IGF-1R antibody A12
Demography
Recurrence

Keywords

  • Circulating tumor cell (CTC)
  • Cixutumumab
  • Extensive disease
  • Small cell lung cancer
  • Vismodegib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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). / Belani, Chandra P.; Dahlberg, Suzanne E.; Rudin, Charles M.; Fleisher, Martin; Chen, Helen X.; Takebe, Naoko; Velasco, Mario R.; Tester, William J.; Sturtz, Keren; Hann, Christine; Shanks, James C.; Monga, Manish; Ramalingam, Suresh S.; Schiller, Joan H.

In: Cancer, 2016.

Research output: Contribution to journalArticle

Belani, CP, Dahlberg, SE, Rudin, CM, Fleisher, M, Chen, HX, Takebe, N, Velasco, MR, Tester, WJ, Sturtz, K, Hann, C, Shanks, JC, Monga, M, Ramalingam, SS & Schiller, JH 2016, '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)', Cancer. https://doi.org/10.1002/cncr.30062
Belani, Chandra P. ; Dahlberg, Suzanne E. ; Rudin, Charles M. ; Fleisher, Martin ; Chen, Helen X. ; Takebe, Naoko ; Velasco, Mario R. ; Tester, William J. ; Sturtz, Keren ; Hann, Christine ; Shanks, James C. ; Monga, Manish ; Ramalingam, Suresh S. ; Schiller, Joan H. / 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). In: Cancer. 2016.
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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 = .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.",
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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 Christine Hann and Shanks, {James C.} and Manish Monga and Ramalingam, {Suresh S.} and Schiller, {Joan H.}",
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T1 - Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer

T2 - A trial of the ECOG-ACRIN Cancer Research Group (E1508)

AU - Belani, Chandra P.

AU - Dahlberg, Suzanne E.

AU - Rudin, Charles M.

AU - Fleisher, Martin

AU - Chen, Helen X.

AU - Takebe, Naoko

AU - Velasco, Mario R.

AU - Tester, William J.

AU - Sturtz, Keren

AU - Hann, Christine

AU - Shanks, James C.

AU - Monga, Manish

AU - Ramalingam, Suresh S.

AU - Schiller, Joan H.

PY - 2016

Y1 - 2016

N2 - 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 = .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.

AB - 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 = .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.

KW - Circulating tumor cell (CTC)

KW - Cixutumumab

KW - Extensive disease

KW - Small cell lung cancer

KW - Vismodegib

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