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Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance).

Publication ,  Journal Article
Hatch, AJ; Sibley, AB; Starr, MD; Brady, JC; Jiang, C; Jia, J; Bowers, DL; Pang, H; Owzar, K; Niedzwiecki, D; Innocenti, F; Venook, AP ...
Published in: Cancer Med
September 2016

Circulating protein markers were assessed in patients with colorectal cancer (CRC) treated with cetuximab in CALGB 80203 to identify prognostic and predictive biomarkers. Patients with locally advanced or metastatic CRC received FOLFOX or FOLFIRI chemotherapy (chemo) or chemo in combination with cetuximab. Baseline plasma samples from 152 patients were analyzed for six candidate markers [epidermal growth factor (EGF), heparin-binding EGF (HBEGF), epidermal growth factor receptor (EGFR), HER2, HER3, and CD73]. Analyte levels were associated with survival endpoints using univariate Cox proportional hazards models. Predictive markers were identified using a treatment-by-marker interaction term in the Cox model. Plasma levels of EGF, HBEGF, HER3, and CD73 were prognostic for overall survival (OS) across all patients (KRAS mutant and wild-type). High levels of EGF predicted for lack of OS benefit from cetuximab in KRAS wild-type (WT) patients (chemo HR = 0.98, 95% CI = 0.74-1.29; chemo+cetuximab HR = 1.54, 95% CI = 1.05-2.25; interaction P = 0.045) and benefit from cetuximab in KRAS mutant patients (chemo HR = 1.72, 95% CI = 1.02-2.92; chemo+cetuximab HR = 0.90, 95% CI = 0.67-1.21; interaction P = 0.026). Across all patients, higher HER3 levels were associated with significant OS benefit from cetuximab treatment (chemo HR = 4.82, 95% CI = 1.68-13.84; chemo+cetuximab HR = 0.95, 95% CI = 0.31-2.95; interaction P = 0.046). CD73 was also identified as predictive of OS benefit in KRAS WT patients (chemo HR = 1.28, 95% CI = 0.88-1.84; chemo+cetuximab HR = 0.60, 95% CI = 0.32-1.13; interaction P = 0.049). Although these results are preliminary, and confirmatory studies are necessary before clinical application, the data suggest that HER3 and CD73 may play important roles in the biological response to cetuximab.

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Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

September 2016

Volume

5

Issue

9

Start / End Page

2249 / 2260

Location

United States

Related Subject Headings

  • ras Proteins
  • Young Adult
  • Prognosis
  • Neoplasm Staging
  • Neoplasm Metastasis
  • Mutation
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Humans
 

Citation

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ICMJE
MLA
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Hatch, A. J., Sibley, A. B., Starr, M. D., Brady, J. C., Jiang, C., Jia, J., … Alliance for Clinical Trials in Oncology. (2016). Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance). Cancer Med, 5(9), 2249–2260. https://doi.org/10.1002/cam4.806
Hatch, Ace J., Alexander B. Sibley, Mark D. Starr, J Chris Brady, Chen Jiang, Jingquan Jia, Daniel L. Bowers, et al. “Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance).Cancer Med 5, no. 9 (September 2016): 2249–60. https://doi.org/10.1002/cam4.806.
Hatch AJ, Sibley AB, Starr MD, Brady JC, Jiang C, Jia J, et al. Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance). Cancer Med. 2016 Sep;5(9):2249–60.
Hatch, Ace J., et al. “Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance).Cancer Med, vol. 5, no. 9, Sept. 2016, pp. 2249–60. Pubmed, doi:10.1002/cam4.806.
Hatch AJ, Sibley AB, Starr MD, Brady JC, Jiang C, Jia J, Bowers DL, Pang H, Owzar K, Niedzwiecki D, Innocenti F, Venook AP, Hurwitz HI, Nixon AB, Alliance for Clinical Trials in Oncology. Blood-based markers of efficacy and resistance to cetuximab treatment in metastatic colorectal cancer: results from CALGB 80203 (Alliance). Cancer Med. 2016 Sep;5(9):2249–2260.
Journal cover image

Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

September 2016

Volume

5

Issue

9

Start / End Page

2249 / 2260

Location

United States

Related Subject Headings

  • ras Proteins
  • Young Adult
  • Prognosis
  • Neoplasm Staging
  • Neoplasm Metastasis
  • Mutation
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Humans