Frequency of S492R mutations in the epidermal growth factor receptor: analysis of plasma DNA from patients with metastatic colorectal cancer treated with panitumumab or cetuximab monotherapy
Open accessAbstract
Background Antibodies against epidermal growth factor receptor (EGFR), panitumumab, a fully human monoclonal antibody, and cetuximab, a human/mouse chimeric monoclonal antibody, have shown clinical efficacy in metastatic colorectal cancer (mCRC). In the phase 3 noninferiority ASPECCT (ClinicalTrials.gov, NCT01001377) study, panitumumab was demonstrated to be noninferior to cetuximab and provided a similar overall survival benefit for patients with chemotherapy-refractory wild-type KRAS exon 2 mCRC. However, some patients eventually develop resistance to anti-EGFR therapy. EGFR p.S492R mutation was previously identified as conferring resistance to cetuximab, but not to panitumumab.Methods This biomarker study analyzed plasma samples from ASPECCT collected at both baseline and posttreatment.Results No EGFR p.S492R mutations were identified at baseline; however, after treatment the EGFR p.S492R mutation was detected in 1% of patients treated with panitumumab versus 16% of those treated with cetuximab, supporting that, in a large population, this mutation is more likely to be induced by cetuximab than by panitumumab. There were, however, no significant differences in progression-free survival or overall survival between patients who were wild-type compared with those with the S492R mutation within the cetuximab arm or the overall population.Conclusions These results may support targeting treatment to small patient subgroups based on the presence of emerging EGFR mutations and provide a molecular rationale for rechallenging with a different anti-EGFR agent in patients who develop resistance. Prospective studies are needed to evaluate the efficacy of panitumumab in the EGFR p.S492R mutant population.
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?
EGFR somatic sequence changes G465R, G465E, S468R and S492R at the extracellular domains confer resistance to cetuximab and panitumumab by preventing monoclonal antibody binding.
“EGFR somatic sequence changes, including G465R, G465E, S468R and S492R, located at the extracellular domains (ECDs) of the EGFR-mAb interaction interface, confer resistance to cetuximab and panitumumab by preventing mAb binding [10, 67, 68].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [68]
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
ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
Van Cutsem, E., Cervantes, A., Adam, R., Sobrero, A., Van Krieken, J. H., Aderka, D., Aranda Aguilar, E., Bardelli, A., Benson, A., Bodoky, G., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw235 · Cited by 3,421 · see citing works
Self-citationPanitumumab–FOLFOX4 Treatment and <i>RAS</i> Mutations in Colorectal Cancer
Douillard, J.-Y., Oliner, K. S., Siena, S., Tabernero, J., Burkes, R., Barugel, M., Humblet, Y., Bodoky, G., Cunningham, D., Jassem, J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1305275 · Cited by 2,263 · see citing works
Self-citationLiquid biopsy: monitoring cancer-genetics in the blood
Crowley, E. H., Nicolantonio, F. D., Loupakis, F., & Bardelli, A. (2013) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.110 · Cited by 1,821 · see citing works
Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients
Siravegna, G., Mussolin, B., Buscarino, M., Corti, G., Cassingena, A., Crisafulli, G., Ponzetti, A., Cremolini, C., Amatu, A., Lauricella, C., et al. (2015) · Nature Medicine · doi:10.1038/nm.3870 · Cited by 1,079 · see citing works
Van Cutsem, E., Lenz, H.-J., Köhne, C.-H., Heinemann, V., Tejpar, S., Melezínek, I., Beier, F., Stroh, C., Rougier, P., van Krieken, J. H., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.4812 · Cited by 789 · see citing works
Sartore-Bianchi, A., Martini, M., Molinari, F., Veronese, S., Nichelatti, M., Artale, S., Di Nicolantonio, F., Saletti, P., De Dosso, S., Mazzucchelli, L., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2466 · Cited by 739 · see citing works
Montagut, C., Dalmases, A., Bellosillo, B., Crespo, M., Pairet, S., Iglesias, M., Salido, M., Gallen, M., Marsters, S., Tsai, S. P., et al. (2012) · Nature Medicine · doi:10.1038/nm.2609 · Cited by 513 · see citing works
Price, T. J., Peeters, M., Kim, T. W., Li, J., Cascinu, S., Ruff, P., Suresh, A. S., Thomas, A., Tjulandin, S., Zhang, K., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70118-4 · Cited by 473 · see citing works
Self-citationAhronian, L. G., Sennott, E. M., Van Allen, E. M., Wagle, N., Kwak, E. L., Faris, J. E., Godfrey, J. T., Nishimura, K., Lynch, K. D., Mermel, C. H., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1518 · Cited by 322 · see citing works
Radinsky, R., Risin, S. A., Fan, D., Dong, Z., Bielenberg, D. R., Bucana, C. D., & Fidler, I. J. (1995) · PubMed · Cited by 321 · see citing works
Taniguchi, K., Uchida, J., Nishino, K., Kumagai, T., Okuyama, T., Okami, J., Higashiyama, M., Kodama, K., Imamura, F., & Kato, K. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1712 · Cited by 315 · see citing works
Detection of Tumor PIK3CA Status in Metastatic Breast Cancer Using Peripheral Blood
Higgins, M. J., Jelovac, D., Barnathan, E., Blair, B., Slater, S. A., Powers, P., Zorzi, J., Jeter, S. C., Oliver, G. R., Fetting, J. H., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2696 · Cited by 307 · see citing works
Arena, S., Bellosillo, B., Siravegna, G., Martínez, A., Cañadas, I., Lazzari, L., Ferruz, N., Russo, M., Misale, S., González, I., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2821 · Cited by 271 · see citing works
Khan, K. H., Cunningham, D., Werner, B., Vlachogiannis, G., Spiteri, I., Heide, T., Fernández-Mateos, J., Vatsiou, A. I., Lampis, A., Darvish-Damavandi, M., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0891 · Cited by 226 · see citing works
Santini, D., Vincenzi, B., Addeo, R., Garufi, C., Masi, G., Scartozzi, M., Mancuso, A. P., Frezza, A. M., Venditti, O., Imperatori, M., et al. (2012) · Annals of Oncology · doi:10.1093/annonc/mdr623 · Cited by 211 · see citing works
Self-citationMontagut, C., Argilés, G., Ciardiello, F., Poulsen, T. T., Dienstmann, R., Kragh, M., Kopetz, S., Lindsted, T., Ding, C., Vidal, J., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2017.5245 · Cited by 135 · see citing works
The road to resistance: EGFR mutation and cetuximab
Bardelli, A., & Janne, P. A. (2012) · Nature Medicine · doi:10.1038/nm.2646 · Cited by 71 · see citing works
Wang, R., Li, X., Zhang, H., Wang, K., & He, J. (2017) · Oncotarget · doi:10.18632/oncotarget.20608 · Cited by 68 · see citing works
BRAF Mutations as Predictive Biomarker for Response to Anti-EGFR Monoclonal Antibodies
van Brummelen, E. M. J., de Boer, A., Beijnen, J. H., & Schellens, J. H. M. (2017) · The Oncologist · doi:10.1634/theoncologist.2017-0031 · Cited by 62 · see citing works
Esposito, C., Rachiglio, A. M., La Porta, M. L., Sacco, A., Roma, C., Iannaccone, A., Tatangelo, F., Forgione, L., Pasquale, R., Barbaro, A., et al. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.26340 · Cited by 53 · see citing works
Liu, X., George, G. C., Tsimberidou, A. M., Naing, A., Wheler, J. J., Kopetz, S., Fu, S., Piha-Paul, S. A., Eng, C., Falchook, G. S., et al. (2015) · BMC Cancer · doi:10.1186/s12885-015-1701-3 · Cited by 52 · see citing works
Kim, T. W., Peeters, M., Thomas, A., Gibbs, P., Hool, K., Zhang, J., Ang, A. L., Bach, B. A., & Price, T. J. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3377 · Cited by 52 · see citing works
Self-citationPeeters, M., Price, T. J., Boedigheimer, M. J., Kim, T. W., Ruff, P., Gibbs, P., Thomas, A., Demonty, G., Hool, K., & Ang, A. L. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2072 · Cited by 39 · see citing works
Self-citationPietrantonio, F., Perrone, F., Biondani, P., Maggi, C., Lampis, A., Bertan, C. M., Venturini, F., Tondulli, L., Ferrari, D., Ricci, V., et al. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.26343 · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy
Li, Q., Geng, S., Luo, H., Wang, W., Mo, Y.-Q., Luo, Q., Wang, L., Song, G.-B., Sheng, J.-P., & Xu, B. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01953-7 · Cited by 546 · see citing works
Zhou, J., Ji, Q., & Li, Q. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02130-2 · Cited by 246 · see citing works
Abbas, N., Mourad, M., Smaily, H., Al Mahmasani, L., & Shamseddine, A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27073265 · Cited by 4 · see citing works
- Authors
- Price, T., Ang, A., Boedigheimer, M., Kim, T. W., Li, J., Cascinu, S., Ruff, P., Satya Suresh, A., Thomas, A., Tjulandin, S., & Peeters, M.
- Affiliations
- Queen Elizabeth Hospital (AU)
- Amgen (United States) (US)
- Asan Medical Center (KR)
- Shanghai East Hospital (CN)
- Marche Polytechnic University (IT)
- University of the Witwatersrand (ZA)
- Department of Medical Oncology, Apollo Hospital, Hyderabad, India
- University of Leicester (GB)
- Russian Cancer Research Center NN Blokhin (RU)
- Antwerp University Hospital (BE)
- Corresponding author
- Price, Timothy
- ORCID
- Venue
- Cancer Biology & Therapy
- Publisher
- Informa UK Limited
- Published
- 2020-10-02
- Volume
- 21
- Issue
- 10
- Pages
- 891-898
- ISSN
- 1538-4047 (ISSN-L)
- 1555-8576
- PMC
- PMC7583702
- OpenAlex
- W3092636333
- Cited by
- 33
- References
- 24
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 8 · 2023: 4 · 2022: 5 · 2021: 5 · 2018: 1 · 2016: 1 · 2015: 2
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cancer Biology & Therapy (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- Amgen Inc (Not Applicable)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- epidermal growth factor receptor, metastatic colorectal cancer, panitumumab, cetuximab, anti-EGFR therapy resistance, plasma DNA, circulating tumor DNA, biomarkers, treatment rechallenge, progression-free survival, overall survival
- MeSH terms
- Cetuximab, Panitumumab, Female, Humans, Male, Mutation, Neoplasm Metastasis, Colorectal Neoplasms, Survival Analysis, ErbB Receptors
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
