TBCRC 001: Comparison and effectiveness of cetuximab alone or cetuximab with carboplatin in women with triple negative, metastatic breast cancer (MBC)

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Purpose of the Study: 

Breast cancers can be categorized by subtypes. This study looked at the subtype referred to as triple negative breast cancer.  Triple negative breast cancer lacks three common characteristics: the estrogen receptor (ER) protein, the progesterone receptor (PR) protein, and the human epidermal growth factor receptor 2 (HER2). Currently available treatments can target each of these markers.  Unfortunately, no such “targeted” therapy has yet been found that is effective in triple negative breast cancer.  Many triple negative breast cancers have been shown to have high expression of another protein, the epidermal growth factor receptor protein (EGFR). Thus, it is hoped that drugs that target that protein may be effective.  Cetuximab is a drug that has been approved for EGFR expressing colon cancer and may be of use in triple negative breast cancer.

TBCRC 001 enrolled 102 women with triple negative, metastatic, (stage 4) breast cancer who were put into groups by chance and assigned to receive cetuximab alone or cetuximab with carboplatin.  Cetuximab was being evaluated to see if it could block the epidermal growth factor pathway and stop the cancer from growing either alone or in combination with the chemotherapy, carboplatin. In addition, the trial collected tumor and blood samples to evaluate the biologic as well as the clinical response. 


National Cancer Institute; Bristol Myers Squibb

Participating Sites: 
  • Baylor College of Medicine
  • Duke University Medical Cancer Center
  • Dana-Farber/ Harvard Cancer Center
  • Georgetown University
  • Indiana University Simon Cancer Center
  • Johns Hopkins University
  • Mayo Clinic Cancer Center
  • MD Anderson Cancer Center
  • University of Alabama, Birmingham
  • University of California, San Francisco
  • University of North Carolina, Chapel Hill
  • Washington University
Start Date & Stop Date: 

Date First Site Activated:  October, 2005
Date Trial Closed to Enrollment:  October, 2007

Key Eligibility Requirements: 
  • Metastatic (stage 4) breast cancer with measurable disease
  • Triple negative (ER negative, PR negative, and HER2 negative)
  • No more than 3 prior chemotherapy regimens
  • No prior EGFR inhibitor or platinum for metastatic disease
  • No significant organ dysfunction
  • Central nervous system (CNS) only if involvement is stable for at least 3 months
  • At least 6 months’ life expectancy
Study Design: 
  • Eligible women were assigned by chance (randomized) as follows:
    • Group 1 - cetuximab alone with carboplatin added when the cancer started to grow
    • Group 2 - combination cetuximab plus carboplatin from the beginning
  • Participating women had their tumors measured every 8 weeks using either CT or MRI scans.
  • Treatment was stopped if the disease was growing, if the side effects were not tolerable, or if patients chose to stop.
  • Willing women were asked to permit biopsies of the tumor before starting therapy, and again 7 days after beginning treatment in order to examine drug impact on the tumor.
  • 102 women enrolled in this trial, and most of their tumors were the triple negative subtype
  • Fewer than 10% responded to the cetuximab alone, which was expected.
  • 18% responded to the combination of cetuximab plus carboplatin
  • 31% of those who responded had their cancer controlled for at least 6 months.  This was better than expected from standard therapy, although not as good as we had hoped.
  • Most patients experienced rapid disease progression with only a 2-month average time before the disease started growing again.
  • Neither treatment caused serious side effects.  Ten percent of women had rash, fatigue and nausea and vomiting that was generally mild.
  • Biopsy and blood samples offered insight into this cancer subtype.
  • 18 women allowed repeated biopsies of their tumors before and after therapy.
  • Interestingly, the women that responded to the anti-EGFR drug showed an EGFR pathway that was turned “on” initially and then turned “off” by the drug. This is exciting because it proves that the drug was doing what it was supposed to in those tumors, and discouraging because so many of the tumors had other ways to grow that this therapy didn’t affect.
Next Steps: 
  • Women who participated in this study have helped to advance our understanding of the disease, moving us forward in the search for markers of cancer activity and better treatment options.
  • It is not likely there will be one best treatment for patients with triple negative breast cancer.
  • Future trials will be developed to examine other characteristics that appear important for triple negative breast cancer.
Scientific Publications Available for this Clinical Trial: 

Carey, L.A., Mayer, E., Marcom, P.K., Rugo, H., Liu, M., Ma, C., Rimawi, M., Storniolo, A., Forero, A., Esteva, F., Wolff, A., Ingle, J., Ferraro, M., Sawyer, L., Davidson, N., Perou, C.M., Winer, E.P.  TBCRC 001: EGFR Inhibition with Cetuximab in Metastatic Triple Negative (Basal-Like) Breast Cancer. 2007 SABCS, Poster #307.

Carey, L.A., Rugo, H.S., Marcom, P.K., Irvin, W., Ferraro, M., Burrows, E., He, X., Perou, C.M., Winer, E.P. (TBCRC). TBCRC 001: EGFR Inhibition with Cetuximab Added to Carboplatin in Metastatic Triple-Negative (Basal-like) Breast Cancer.  2008 ASCO, Oral Presentation, Abstract #1009.

Rugo, H.S., Carey, L.A., Mayer, E., Burrows, E., Scott, J., Moore, D., Park, J.W. (TBCRC).  Assays of Circulating Tumor Cells and Outcome in the Triple Negative Breast Cancer Trial TBCRC 001.  2008 Molecular Markers, Poster, Abstract #2.

Carey, L., O’Shaughnessy, J.A., Hoadley, K., Khambata-Ford, S., Horak, C.E., Xu, L., Awad, M., Brickman, D., Muller, S., Donato, J., Asmar, L., Stiljeman, I., Ebbert, M., Bernard, P., Perou, C.M. Potential predictive markers of benefit from cetuximab in metastatic breast cancer: an analysis of two randomized Phase 2 trials. 2009 SABCS, Poster.

Carey, L.A., Rugo, H.S., Marcom, P.K., Mayer, E.L., Esteva, F.J., Ma, C.X., Liu, M.C., Storniolo, A.M., Rimawi, M.F., Forero-Torres, A., Wolff, A.C., Hobday, T.J., Ivanova, A., Chiu, W., Ferraro, M., Burrows, E., Bernard, P.S., Hoadley, K.A., Perou, C.M., Winer, E.P. TBCRC 001: Randomized Phase II Study of Cetuximab in Combination With Carboplatin in Stage IV Triple-Negative Breast Cancer. J Clin Oncol 30 (21): 2012.

Tao, J., Castel, P., Radosevic-Robin, N., Elkabets, M., Auricchio, N., Aceto, N., Weitsman, G., Barber, P., Vojnovic, B., Ellis, H., Morse,  N.,  Viola-Villegas, N.T., Campos, A.B., Juric, D., Hazra, S., Singh, S., Kim, P.,  Bergamaschi, S., Maheswaran, S., Ng, T., Penault-Llorca, F., Lewis, J.S., Carey, L.A., Perou, C.M., Baselga, J., Scaltriti, M. Antagonism of EGFR and HER3 enhances the response to inhibitors of the PI3K/Akt pathway in triple negative breast cancer. Science Signaling 7 (318): 2014

Magbanua, M.J.M., Carey, L.A., DeLuca, A., Hwang, J., Scott, J.H., Rimawi, M.F., Mayer, E.L., Marcom, P.K., Liu, M.C., Esteva, F.J., Park, J.W., Rugo, H.S. Circulating tumor cell analysis in metastatic triple-negative breast cancers. Clinical Cancer Research 21 (5): 2015.

 *This summary was reviewed by: Lisa Carey, M.D.  This summary was also reviewed and approved by the members of the TBCRC Patient Advocate Working Group.