TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer
Open accessAbstract
PURPOSE: Epidermal growth factor receptor (EGFR) is a targetable receptor frequently overexpressed in basal-like breast cancer, which comprises most triple-negative breast cancers (TNBCs), the only subtype without established targeted therapy. PATIENTS AND METHODS: In this randomized phase II trial, patients with metastatic TNBC received anti-EGFR antibody cetuximab (400 mg/m(2) load then 250 mg/m(2) per week intravenously [IV]) alone, with carboplatin (area under the curve of 2, once per week IV) added after progression or as concomitant therapy from the beginning. Response rate (RR) was the primary end point; others included time to progression (TTP), overall survival (OS), and toxicity. Embedded correlative studies included molecular subtyping on archival tissue. Fresh tumor tissue before and after 7 to 14 days of therapy was used for microarray analyses exploring EGFR pathway activity and inhibition. RESULTS: In 102 patients with TNBC, RRs were 6% (two of 31) to cetuximab and 16% (four of 25) to cetuximab plus carboplatin after progression. RR to those treated from the beginning with cetuximab plus carboplatin was 17% (12 of 71); 31% of patients responded or had prolonged disease stabilization. The cetuximab plus carboplatin regimen was well tolerated, but both TTP and OS were short at 2.1 months (95% CI, 1.8 to 5.5 months) and 10.4 months (95% CI, 7.7 to 13.1 months), respectively. Of 73 patients with archival tissue for analysis, 74% had basal-like molecular subtype. Sixteen patients had tumor biopsies before and 1 week after therapy; genomic patterns of the EGFR pathway showed activation in 13 and inhibition by therapy in five. CONCLUSION: Despite strong preclinical data, combination cetuximab plus carboplatin in metastatic TNBC produced responses in fewer than 20% of patients. EGFR pathway analysis showed that most TNBCs involved activation. However, cetuximab blocked expression of the EGFR pathway in only a minority, suggesting that most had alternate mechanisms for pathway activation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Ongoing clinical trials for metastatic TNBC include platinum agents in their treatment regimens.
“Furthermore, ongoing clinical trials for metastatic TNBC are including platinum agents in their treatment regimens (4, 36–38).”
From Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model (2015) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular portraits of human breast tumours
Perou, C., Sørlie, T., Eisen, M., van de Rijn, M., Jeffrey, S., Rees, C. A., Pollack, J., Ross, D., Johnsen, H., Akslen, L., et al. (2000) · Nature · doi:10.1038/35021093 · Cited by 16,551 · see citing works
Self-citationSørlie, T., Perou, C., Tibshirani, R., Aas, T., Geisler, S., Johnsen, H., Hastie, T., Eisen, M., van de Rijn, M., Jeffrey, S., et al. (2001) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.191367098 · Cited by 11,695 · see citing works
Self-citationRepeated observation of breast tumor subtypes in independent gene expression data sets
Sørlie, T., Tibshirani, R. J., Parker, J. S., Hastie, T. J., Marron, J. S., Nobel, A. B., Deng, S., Johnsen, H., Pesich, R., Geisler, S. B., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0932692100 · Cited by 5,428 · see citing works
Self-citationSupervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes
Parker, J. S., Mullins, M., Cheang, M. C. U., Leung, S. C. Y., Voduc, D. K., Vickery, T. L., Davies, S. R., Fauron, C. M. ‐., He, X., Hu, Z., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.1370 · Cited by 4,737 · see citing works
Self-citationCirculating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer
Cristofanilli, M., Budd, G. T., Ellis, M. J., Stopeck, A., Matera, J., Miller, M. C., Reuben, J. M., Doyle, G. V., Allard, W. J., Terstappen, L. W. M. M., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040766 · Cited by 4,602 · see citing works
Race, Breast Cancer Subtypes, and Survival in the Carolina Breast Cancer Study
Carey, L., Perou, C. M., Livasy, C., Dressler, L. G., Cowan, D., Conway, K., Karaca, G., Troester, M. A., Tse, C. K., Edmiston, S. N., et al. (2006) · JAMA · doi:10.1001/jama.295.21.2492 · Cited by 3,810 · see citing works
Self-citationOptimal two-stage designs for phase II clinical trials.
Simon, R. (1989) · Controlled Clinical Trials · doi:10.1016/0197-2456(89)90015-9 · Cited by 3,636 · see citing works
Nielsen, T. O., Hsu, F. D., Jensen, K. C., Cheang, M. C. U., Karaca, G., Hu, Z., Hernandez‐Boussard, T., Livasy, C., Cowan, D., Dressler, L. G., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0220 · Cited by 2,665 · see citing works
Self-citationPhenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer
Prat, A., Parker, J. S., Karginova, O. A., Fan, C., Livasy, C., Herschkowitz, J. I., He, X., & Perou, C. M. (2010) · Breast Cancer Research · doi:10.1186/bcr2635 · Cited by 2,164 · see citing works
Self-citationThe Triple Negative Paradox: Primary Tumor Chemosensitivity of Breast Cancer Subtypes
Carey, L., Dees, E. C., Sawyer, L., Gatti, L., Moore, D. T., Collichio, F. A., Ollila, D. W., Sartor, C. I., Graham, M. L., & Perou, C. M. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1109 · Cited by 2,086 · see citing works
Self-citationSotiriou, C. P., Neo, S.-Y., McShane, L. M., Korn, E. L., Long, P. M., Jazaeri, A. A., Martiat, P., Fox, S. B., Harris, A. L., & Liu, E. T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1732912100 · Cited by 1,993 · see citing works
The molecular portraits of breast tumors are conserved across microarray platforms
Hu, Z., Fan, C., Oh, D. S., Marron, J. S., He, X., Qaqish, B. F., Livasy, C., Carey, L., Reynolds, E. R., Dressler, L. G., et al. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-96 · Cited by 1,492 · see citing works
Self-citationGene-Expression Signatures in Breast Cancer
Sotiriou, C. P., & Pusztai, L. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0801289 · Cited by 1,482 · see citing works
Deconstructing the molecular portraits of breast cancer
Prat, A., & Perou, C. M. (2010) · Molecular Oncology · doi:10.1016/j.molonc.2010.11.003 · Cited by 1,345 · see citing works
Self-citationHerschkowitz, J. I., Simin, K. J., Weigman, V., Mikaelian, I., Usary, J., Hu, Z., Rasmussen, K., Jones, L. P., Assefnia, S., Chandrasekharan, S., et al. (2007) · Genome biology · doi:10.1186/gb-2007-8-5-r76 · Cited by 1,287 · see citing works
Self-citationEfficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer
Silver, D. P., Richardson, A. L., Eklund, A. C., Wang, Z. C., Szállási, Z., Li, Q., Birkbak, N. J., Leong, C.-O., Calogrias, D., Buraimoh, A., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.4725 · Cited by 982 · see citing works
Self-citationEllis, M. J., Tao, Y., Luo, J. R., A’Hern, R., Evans, D. B., Bhatnagar, A. S., Ross, H. A. C., von Kameke, A., Miller, W. R., Smith, I., et al. (2008) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djn309 · Cited by 654 · see citing works
HER2 and Response to Paclitaxel in Node-Positive Breast Cancer
Hayes, D. F., Thor, A. D., Dressler, L. G., Weaver, D. L., Edgerton, S. M., Cowan, D., Broadwater, G., Goldstein, L. J., Martino, S., Ingle, J. N., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa071167 · Cited by 607 · see citing works
Self-citationByrski, T., Gronwald, J., Huzarski, T., Grzybowska, E. A., Budryk, M., Stawicka, M., Mierzwa, T., Szwiec, M., Wiśniowski, R., Siołek, M., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.7019 · Cited by 515 · see citing works
Bergamaschi, A., Kim, Y. H., Wang, P., Sørlie, T., Hernandez‐Boussard, T., Lønning, P. E., Tibshirani, R. J., Børresen‐Dale, A., & Pollack, J. R. (2006) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20366 · Cited by 506 · see citing works
Hoeflich, K. P., O'Brien, C. L., Boyd, Z. S., Cavet, G., Guerrero, S., Jung, K., Januario, T., Savage, H. M., Punnoose, E. A., Truong, T., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0317 · Cited by 467 · see citing works
Mirzoeva, O. K., Das, D., Heiser, L. M., Bhattacharya, S., Siwak, D. R., Gendelman, R., Bayani, N., Wang, N. J., Neve, R. M., Guan, Y., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3389 · Cited by 387 · see citing works
O’Neil, B. H., Allen, R., Spigel, D. R., Stinchcombe, T. E., Moore, D. T., Berlin, J. D., & Goldberg, R. M. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.11.7812 · Cited by 360 · see citing works
André, F., Job, B., Dessen, P., Tordai, A., Michiels, S., Liedtke, C., Richon, C., Yan, K., Wang, B., Vassal, G., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1791 · Cited by 336 · see citing works
EGFR associated expression profiles vary with breast tumor subtype
Hoadley, K. A., Weigman, V., Fan, C., Sawyer, L., He, X., Troester, M. A., Sartor, C. I., Rieger-House, T., Bernard, P. S., Carey, L., et al. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-258 · Cited by 278 · see citing works
Self-citationPlatinum-based chemotherapy in metastatic breast cancer: current status
Decatris, M. P., Sundar, S., & O'Byrne, K. J. (2003) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(03)00139-7 · Cited by 212 · see citing works
Berger, V. W., Ivanova, A., & Knoll, M. D. (2003) · Statistics in Medicine · doi:10.1002/sim.1538 · Cited by 200 · see citing works
Self-citationManagement of advanced breast cancer with the epothilone B analog, ixabepilone
Gradishar, W. J. (2009) · Drug Design Development and Therapy · doi:10.2147/dddt.s3122 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Carey LA, O'Shaughnessy J, Hoadley KA, et al: Potential predictive markers of cetuximab ben- efit in metastatic triple negative breast cancer: An analysis of two randomized phase II trials. Pre- sented at the 32nd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 9-13, 2009
Cited by
Sorted by citations
Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease
Bianchini, G., Balko, J. M., Mayer, I. A., Sanders, M. E., & Gianni, L. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.66 · Cited by 3,079 · see citing works
Proteogenomics connects somatic mutations to signalling in breast cancer
CPTAC, N., Mertins, P., Mani, D. R., Ruggles, K. V., Gillette, M. A., Clauser, K. R., Wang, P., Wang, X., Qiao, J. W., Cao, S., et al. (2016) · Nature · doi:10.1038/nature18003 · Cited by 1,676 · see citing works
Self-citationPembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Nanda, R., Chow, L. Q. M., Dees, E. C., Berger, R., Gupta, S., Geva, R., Pusztai, L., Pathiraja, K., Aktan, G., Cheng, J. D., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.8931 · Cited by 1,477 · see citing works
Tan, T. Z., Miow, Q. H., Miki, Y., Noda, T., Mori, S., Huang, R. Y., & Thiery, J. P. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201404208 · Cited by 792 · see citing works
Targeted therapy for breast cancer and molecular mechanisms of resistance to treatment
Gu, G., Dustin, D., & Fuqua, S. A. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.11.005 · Cited by 163 · see citing works
Guestini, F., McNamara, K. M., Ishida, T., & Sasano, H. (2016) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1125469 · Cited by 58 · see citing works
Identification of synergistic drug combinations using breast cancer patient-derived xenografts
Turner, T. H., Alzubi, M. A., & Harrell, J. C. (2020) · Scientific Reports · doi:10.1038/s41598-020-58438-0 · Cited by 50 · see citing works
Tonsing-Carter, E., Bailey, B. J., Saadatzadeh, M. R., Ding, J., Wang, H., Sinn, A. L., Peterman, K. M., Spragins, T. K., Silver, J. M., Sprouse, A. A., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0237 · Cited by 42 · see citing works
Cruz-Gordillo, P., Honeywell, M. E., Harper, N. W., Leete, T., & Lee, M. J. (2020) · Science Signaling · doi:10.1126/scisignal.abb9820 · Cited by 24 · see citing works
- Authors
- 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.-K., Ferraro, M., Burrows, E., Bernard, P. S., Hoadley, K. A., Perou, C. M., & Winer, E. P.
- Affiliations
- Lisa A. Carey, Anastasia Ivanova, Wing-Keung Chiu, Madlyn Ferraro, Emily Burrows, Katherine A. Hoadley, and Charles M. Perou, University of North Carolina at Chapel Hill, Chapel Hill; P. Kelly Marcom, Duke University, Durham, NC; Hope S. Rugo, University of California at San Francisco, San Francisco, CA; Erica L. Mayer, Dana-Farber Cancer Institute, Boston, MA; Francisco J. Esteva, The University of Texas MD Anderson Cancer Center; Mothaffar F. Rimawi, Baylor University College of Medicine, Houston, TX;...
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2012-07-20
- Volume
- 30
- Issue
- 21
- Pages
- 2615-2623
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC3413275
- OpenAlex
- W2153769134
- Cited by
- 499
- References
- 28
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 23 · 2023: 20 · 2022: 31 · 2021: 40 · 2020: 32 · 2019: 40 · 2018: 33 · 2017: 46 · 2016: 50 · 2015: 55 · 2014: 36 · 2013: 44 · 2012: 12
- FWCI
- 15.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Avon Foundation for Women
- Breast Cancer Research Foundation
- Bristol-Myers Squibb
- Translational Breast Cancer Research Consortium
- National Institutes of Health (CA58223)
- National Cancer Institute (CA-58223, P50CA058223)
- National Center for Research Resources (M01 RR00046, M01RR000046, UL1RR024148)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Keywords
- cetuximab, carboplatin, triple-negative breast cancer, metastatic breast cancer, EGFR signaling, epidermal growth factor receptor, basal-like breast cancer, anti-EGFR antibody therapy, combination chemotherapy, molecular subtyping, response rate, overall survival
- MeSH terms
- Cetuximab, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Female, Humans, Middle Aged, Neoplasm Staging, Receptors, Estrogen, Receptors, Progesterone, Biomarkers, Tumor, Signal Transduction, Survival Analysis, Carboplatin, Treatment Outcome, Disease Progression, Erb-b2 Receptor Tyrosine Kinases, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
