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Cited by 253

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge

Open access
Parseghian, C.M., Loree, J.M., Morris, V.K., Liu, X., Clifton, K.K., Napolitano, S., Henry, J.T., Pereira, A.A., Vilar, E., Johnson, B., Kee, B., Raghav, K., Dasari, A., Wu, J., Garg, N., Raymond, V.M., Banks, K.C., Talasaz, A.A., Lanman, R.B., Strickler, J.H., Hong, D.S., Corcoran, R.B., Overman, M.J., Kopetz, S.·2019·Annals of Oncology
DOI 10.1093/annonc/mdy509
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Abstract

BACKGROUND: Colorectal cancer (CRC) has been shown to acquire RAS and EGFR ectodomain mutations as mechanisms of resistance to epidermal growth factor receptor (EGFR) inhibition (anti-EGFR). After anti-EGFR withdrawal, RAS and EGFR mutant clones lack a growth advantage relative to other clones and decay; however, the kinetics of decay remain unclear. We sought to determine the kinetics of acquired RAS/EGFR mutations after discontinuation of anti-EGFR therapy. PATIENTS AND METHODS: We present the post-progression circulating tumor DNA (ctDNA) profiles of 135 patients with RAS/BRAF wild-type metastatic CRC treated with anti-EGFR who acquired RAS and/or EGFR mutations during therapy. Our validation cohort consisted of an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling. A separate retrospective cohort of 80 patients was used to evaluate overall response rate and progression free survival during re-challenge therapies. RESULTS: Our analysis showed that RAS and EGFR relative mutant allele frequency decays exponentially (r2=0.93 for RAS; r2=0.94 for EGFR) with a cumulative half-life of 4.4 months. We validated our findings using an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling, confirming exponential decay with an estimated half-life of 4.3 months. A separate retrospective cohort of 80 patients showed that patients had a higher overall response rate during re-challenge therapies after increasing time intervals, as predicted by our model. CONCLUSION: These results provide scientific support for anti-EGFR re-challenge and guide the optimal timing of re-challenge initiation.

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Metadata

Authors
Parseghian, C. M., Loree, J. M., Morris, V. K., Liu, X., Clifton, K. K., Napolitano, S., Henry, J. T., Pereira, A. A., Vilar, E., Johnson, B., Kee, B., Raghav, K., Dasari, A., Wu, J., Garg, N., Raymond, V. M., Banks, K. C., Talasaz, A. A., Lanman, R. B., Strickler, J. H., Hong, D. S., Corcoran, R. B., Overman, M. J., & Kopetz, S.
Venue
Annals of Oncology
Publisher
Elsevier BV
Published
2019-02
Volume
30
Issue
2
Pages
243-249
ISSN
0923-7534 (ISSN-L)
DOI
10.1093/annonc/mdy509
OpenAlex
W2901367407
Cited by
253
References
30
FWCI
8.09
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge. https://app.cochat.ai/papers/10.1093/annonc/mdy509
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Parseghian, C. M., Loree, J. M., Morris, V. K., Liu, X., Clifton, K. K., Napolitano, S., Henry, J. T., Pereira, A. A., Vilar, E., Johnson, B., Kee, B., Raghav, K., Dasari, A., Wu, J., Garg, N., Raymond, V. M., Banks, K. C., Talasaz, A. A., Lanman, R. B., . . . Kopetz, S. (2019). Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge. Annals of Oncology. https://doi.org/10.1093/annonc/mdy509

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.