Rechallenge for Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer With Acquired Resistance to First-line Cetuximab and Irinotecan: A Phase 2 Single-Arm Clinical Trial
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Importance: Based on a small retrospective study, rechallenge with cetuximab-based therapy for patients with KRAS wild-type metastatic colorectal cancer (mCRC) who were previously treated with the same anti-epidermal growth factor receptor-based regimen might be efficacious. Recent data suggest the role of liquid biopsy as a tool to track molecular events in circulating tumor DNA (ctDNA). Objective: To prospectively assess the activity of cetuximab plus irinotecan as third-line treatment for patients with RAS and BRAF wild-type mCRC who were initially sensitive to and then resistant to first-line irinotecan- and cetuximab-based therapy. Design, Setting, and Participants: Multicenter phase 2 single-arm trial conducted from January 7, 2015, to June 19, 2017. Liquid biopsies for analysis of ctDNA were collected at baseline. Main eligibility criteria included RAS and BRAF wild-type status on tissue samples; prior first-line irinotecan- and cetuximab-based regimen with at least partial response, progression-free survival of at least 6 months with first-line therapy, and progression within 4 weeks after last dose of cetuximab; and prior second-line oxaliplatin- and bevacizumab-based treatment. Interventions: Biweekly cetuximab, 500 mg/m2, plus irinotecan, 180 mg/m2. Main Outcomes and Measures: Overall response rate according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included progression-free survival and overall survival and, as an exploratory analysis, RAS mutations in ctDNA. Results: Twenty-eight patients (9 women and 19 men; median age, 69 years [range, 45-79 years]) were enrolled. Six partial responses (4 confirmed) and 9 disease stabilizations were reported (response rate, 21%; 95% CI, 10%-40%; disease control rate, 54%; 95% CI, 36%-70%). Primary end point was met because lower limit of 95% CI of response rate was higher than 5%. RAS mutations were found in ctDNA collected at rechallenge baseline in 12 of 25 evaluable patients (48%). No RAS mutations were detected in samples from patients who achieved confirmed partial response. Patients with RAS wild-type ctDNA had significantly longer progression-free survival than those with RAS mutated ctDNA (median progression-free survival, 4.0 vs 1.9 months; hazard ratio, 0.44; 95% CI, 0.18-0.98; P = .03). Conclusions and Relevance: This is the first prospective demonstration that a rechallenge strategy with cetuximab and irinotecan may be active in patients with RAS and BRAF wild-type mCRC with acquired resistance to first-line irinotecan- and cetuximab-based therapy. The evaluation of RAS mutational status on ctDNA might be helpful in selecting candidate patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02296203.
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BRAF mutation is a powerful biomarker of poor prognosis for metastatic colorectal cancer patients receiving anti-EGFR monoclonal antibodies.
“BRAF mutation is a powerful biomarker of poor prognosis for mCRC patients receiving anti-EGFR mAbs [80, 91, 92].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [91]
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New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534 · see citing works
The National Comprehensive Cancer Network
McGivney, W. T. (1998) · Cancer · doi:10.1002/(sici)1097-0142(19980515)82:10+ · Cited by 16,760 · see citing works
Cook, R. J., Dickens, B. M., & Fathalla, M. F. (2003) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199241323.003.0025 · Cited by 10,813 · see citing works
Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration
Thorvaldsdottir, H., Robinson, J. T., & Mesirov, J. P. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbs017 · Cited by 9,049 · see citing works
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-citationTournigand, C., André, T., Achille, E., Lledo, G., Flesh, M., Mery-Mignard, D., Quinaux, E., Couteau, C., Buyse, M., Ganem, G., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.05.113 · Cited by 2,915 · see citing works
Grothey, A., Cutsem, E. V., Sobrero, A., Siena, S., Falcone, A., Ychou, M., Humblet, Y., Bouché, O., Mineur, L., Barone, C., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61900-x · Cited by 2,895 · see citing works
Self-citationOverman, M. J., McDermott, R., Leach, J. L., Lonardi, S., Lenz, H.-J., Morse, M. A., Desai, J., Hill, A., Axelson, M., Moss, R. A., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30422-9 · Cited by 2,836 · see citing works
Self-citationOverman, M. J., Lonardi, S., Wong, K. Y. M., Lenz, H.-J., Gelsomino, F., Aglietta, M., Morse, M. A., Van Cutsem, E., McDermott, R., Hill, A., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.76.9901 · Cited by 2,079 · see citing works
Self-citationCOSMIC: somatic cancer genetics at high-resolution
Forbes, S. A., Beare, D., Boutselakis, H., Bamford, S., Bindal, N., Tate, J., Cole, C. G., Ward, S., Dawson, E., Ponting, L., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1121 · Cited by 1,922 · see citing works
Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
Misale, S., Yaeger, R., Hobor, S., Scala, E., Janakiraman, M., Liska, D., Valtorta, E., Schiavo, R., Buscarino, M., Siravegna, G., et al. (2012) · Nature · doi:10.1038/nature11156 · Cited by 1,889 · see citing works
The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers
Diaz Jr, L. A., Williams, R. T., Wu, J., Kinde, I., Hecht, J. R., Berlin, J., Allen, B., Bozic, I., Reiter, J. G., Nowak, M. A., et al. (2012) · Nature · doi:10.1038/nature11219 · Cited by 1,713 · see citing works
Randomized Trial of TAS-102 for Refractory Metastatic Colorectal Cancer
Mayer, R. J., Van Cutsem, E., Falcone, A., Yoshino, T., Garcia-Carbonero, R., Mizunuma, N., Yamazaki, K., Shimada, Y., Tabernero, J., Komatsu, Y., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414325 · Cited by 1,431 · see citing works
Self-citationHiggins (2002) · doi:10.1002/(issn)1097-0258 · Cited by 1,248 · 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
Self-citationSartore-Bianchi, A., Trusolino, L., Martino, C., Bencardino, K., Lonardi, S., Bergamo, F., Zagonel, V., Leone, F., Depetris, I., Martinelli, E., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)00150-9 · Cited by 1,016 · see citing works
Self-citationOne-Sample Multiple Testing Procedure for Phase II Clinical Trials
Fleming, T. R. (1982) · Biometrics · doi:10.2307/2530297 · Cited by 1,004 · see citing works
Sobrero, A. F., Maurel, J., Fehrenbacher, L., Scheithauer, W., Abubakr, Y. A., Lutz, M. P., Vega-Villegas, M. E., Eng, C., Steinhauer, E. U., Prausová, J., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.1193 · Cited by 940 · see citing works
Drilon, A. E. D. C., Siena, S., Ou, S. I., Patel, M. R., Ahn, M., Lee, J., Bauer, T. M., Farago, A. F., Wheler, J. J., Liu, S. V., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1237 · Cited by 827 · see citing works
Li, J., Qin, S., Xu, R., Yau, T. C. C., Ma, B., Pan, H., Xu, J., Bai, Y., Chi, Y., Wang, L., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70156-7 · Cited by 813 · see citing works
Tumour heterogeneity and the evolution of polyclonal drug resistance
Burrell, R. A., & Swanton, C. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.06.005 · Cited by 417 · see citing works
Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer
Russo, M., Siravegna, G., Blaszkowsky, L. S., Corti, G., Crisafulli, G., Ahronian, L. G., Mussolin, B., Kwak, E. L., Buscarino, M., Lazzari, L., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1283 · Cited by 402 · see citing works
Sample size tables for exact single‐stage phase II designs
A’Hern, R. (2001) · Statistics in Medicine · doi:10.1002/sim.721 · Cited by 400 · 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
Xu, J., Kim, T. W., Shen, L., Sriuranpong, V., Pan, H., Xu, R., Guo, W., Han, S., Liu, T., Park, Y. S., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.3245 · Cited by 266 · see citing works
Bianchi, A. S., Ardini, E., Bosotti, R., Amatu, A., Valtorta, E., Somaschini, A., Raddrizzani, L., Palmeri, L., Banfi, P., Bonazzina, E. F., et al. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv306 · Cited by 245 · see citing works
Acquired RAS or EGFR mutations and duration of response to EGFR blockade in colorectal cancer
Van Emburgh, B. O., Arena, S., Siravegna, G., Lazzari, L., Crisafulli, G., Corti, G., Mussolin, B., Baldi, F., Buscarino, M., Bartolini, A., et al. (2016) · Nature Communications · doi:10.1038/ncomms13665 · Cited by 214 · see citing works
Self-citationSantini, 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-citationPietrantonio, F., Vernieri, C., Siravegna, G., Mennitto, A., Berenato, R., Perrone, F., Gloghini, A., Tamborini, E., Lonardi, S., Morano, F., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1863 · Cited by 182 · 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
Cremolini, C., Morano, F., Moretto, R., Berenato, R., Tamborini, E., Perrone, F., Rossini, D., Gloghini, A., Busico, A., Zucchelli, G., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx546 · Cited by 122 · see citing works
Self-citationXu, J.-M., Wang, Y., Wang, Y., Wang, Y., Liu, T., Ni, M., Li, M., Li, L., Ge, F.-J., Gong, C., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2738 · Cited by 76 · see citing works
Salvatore, L., Aprile, G., Arnoldi, E., Aschele, C., Carnaghi, C., Cosimelli, M., Maiello, E., Normanno, N., Sciallero, S., Valvo, F., et al. (2017) · ESMO Open · doi:10.1136/esmoopen-2016-000147 · Cited by 51 · see citing works
Self-citationAKT 1 and BRAF mutations in pediatric aggressive fibromatosis
Meazza, C., Belfiore, A., Busico, A., Settanni, G., Paielli, N., Cesana, L., Ferrari, A., Chiaravalli, S., Massimino, M., Gronchi, A., et al. (2016) · Cancer Medicine · doi:10.1002/cam4.669 · Cited by 36 · see citing works
Self-citationEmergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer
Oddo, D., Siravegna, G., Gloghini, A., Vernieri, C., Mussolin, B., Morano, F., Crisafulli, G., Berenato, R., Corti, G., Volpi, C. C., et al. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.196 · Cited by 36 · see citing works
Self-citation
Flagged first, then by citations
2 of the 38 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- ClinVar. https://www.ncbi.nlm.nih.gov/clinvar/. Accessed June 15, 2018.
Cited by
Sorted by citations
Cervantes, A., Adam, R., Roselló, S., Arnold, D., Normanno, N., Taïeb, J., Seligmann, J., De Baere, T., Osterlund, P., Yoshino, T., et al. (2023) · Annals of Oncology · doi:10.1016/j.annonc.2022.10.003 · Cited by 1,796 · see citing works
Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
Benson, A. B., Venook, A. P., Al-Hawary, M. M., Arain, M. A., Chen, Y., Ciombor, K. K., Cohen, S. A., Cooper, H. S., Deming, D. A., Farkas, L. M., et al. (2021) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2021.0012 · Cited by 1,709 · see citing works
Pascual, J., Attard, G., Bidard, F.-C., Curigliano, G., De Mattos-Arruda, L., Diehn, M., Italiano, A., Lindberg, J., Merker, J. D., Montagut, C., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.05.520 · Cited by 783 · see citing works
Circulating tumor DNA and liquid biopsy in oncology
Cescon, D. W., Bratman, S. V., Chan, S. M., & Siu, L. L. (2020) · Nature Cancer · doi:10.1038/s43018-020-0043-5 · Cited by 600 · see citing works
Clinical management of metastatic colorectal cancer in the era of precision medicine
Ciardiello, F., Ciardiello, D., Martini, G., Napolitano, S., Tabernero, J. M., & Cervantes, A. M. R. (2022) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21728 · Cited by 537 · see citing works
Trifluridine–tipiracil and bevacizumab in refractory metastatic colorectal cancer
Prager, G. W., Taieb, J., Fakih, M., Ciardiello, F., Van Cutsem, E., Elez, E., Cruz, F. M., Wyrwicz, L., Stroyakovskiy, D., Pápai, Z., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2214963 · Cited by 467 · see citing works
Self-citationEng, C., Yoshino, T., Ruíz‐García, E., Mostafa, N., Cann, C., O’Brian, B., Benny, A., Perez, R. O., & Cremolini, C. (2024) · The Lancet · doi:10.1016/s0140-6736(24)00360-x · Cited by 480 · see citing works
Self-citationTreatment sequencing in metastatic colorectal cancer
Modest, D. P., Pant, S., & Bianchi, A. S. (2019) · European Journal of Cancer · doi:10.1016/j.ejca.2018.12.019 · Cited by 328 · see citing works
Immunotherapy of colorectal cancer: Challenges for therapeutic efficacy
Ciardiello, D., Vitiello, P. P., Cardone, C., Martini, G., Troiani, T., Martinelli, E., & Ciardiello, F. (2019) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2019.04.003 · Cited by 303 · see citing works
ctDNA as a cancer biomarker: A broad overview
Pessoa, L. S., Heringer, M., & Ferrer, V. P. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.103109 · Cited by 303 · see citing works
Using Circulating Tumor DNA in Colorectal Cancer: Current and Evolving Practices
Malla, M., Loree, J. M., Kasi, P. M., & Parikh, A. R. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.21.02615 · Cited by 305 · see citing works
Bianchi, A. S., Pietrantonio, F., Lonardi, S., Mussolin, B., Rua, F., Crisafulli, G., Bartolini, A., Fenocchio, E., Amatu, A., Manca, P., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01886-0 · Cited by 282 · see citing works
Self-citationCirculating tumor DNA to monitor treatment response in solid tumors and advance precision oncology
Bartolomucci, A., de Nóbrega, M., Ferrier, S. T., Dickinson, K., Kaorey, N., Nadeau, A., Castillo, A., & Burnier, J. V. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-00876-y · Cited by 287 · 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
Precision oncology in metastatic colorectal cancer — from biology to medicine
Nicolantonio, F. D., Vitiello, P. P., Marsoni, S., Siena, S., Tabernero, J. M., Trusolino, L., Bernards, R., & Bardelli, A. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00495-z · Cited by 238 · see citing works
Martinelli, E., Ciardiello, D., Martini, G., Troiani, T., Cardone, C., Vitiello, P. P., Normanno, N., Rachiglio, A. M., Maiello, E., Latiano, T., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2019.10.007 · Cited by 225 · see citing works
Yoshino, T., Di Bartolomeo, M., Raghav, K., Masuishi, T., Loupakis, F., Kawakami, H., Yamaguchi, K., Nishina, T., Wainberg, Z., Elez, E., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38032-4 · Cited by 178 · see citing works
Peng, Y., Mei, W., Ma, K., & Zeng, C. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.763790 · Cited by 167 · see citing works
Therapeutic landscape and future direction of metastatic colorectal cancer
Bando, H., Ohtsu, A., & Yoshino, T. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00736-1 · Cited by 146 · see citing works
Rolfo, C. D., Cardona, A. F., Cristofanilli, M., Paz-Ares, L. G., Díaz‐Mochon, J. J., Durán, I., Raez, L. E., Russo, A., Lorente, J. A., Malapelle, U., et al. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2020.102978 · Cited by 139 · see citing works
Current Targeted Therapy for Metastatic Colorectal Cancer
Ohishi, T., Kaneko, M. K., Yoshida, Y., Takashima, A., Kato, Y., & Kawada, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021702 · Cited by 130 · see citing works
Recent developments in immunotherapy for gastrointestinal tract cancers
Chong, X., Madeti, Y., Cai, J., Li, W., Cong, L., Lu, J., Mo, L., Liu, H., He, S., Yu, C., et al. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01578-x · Cited by 129 · see citing works
Parseghian, C. M., Napolitano, S., Loree, J. M., & Kopetz, S. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0823 · Cited by 121 · see citing works
Li, Q.-H., Wang, Y.-Z., Tu, J., Liu, C.-W., Yuan, Y.-J., Lin, R., He, W.-L., Cai, S.-R., He, Y.-L., & Ye, J.-N. (2020) · Gastroenterology Report · doi:10.1093/gastro/goaa026 · Cited by 119 · see citing works
Pinzani, P., D’Argenio, V., Re, M. D., Pellegrini, C., Cucchiara, F., Salvianti, F., & Galbiati, S. (2021) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2020-1685 · Cited by 118 · see citing works
Lan, H., Liu, Y., Liu, J., Wang, X., Guan, Z., Du, J., & Jin, K. (2021) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00961 · Cited by 112 · see citing works
Effects of Metastatic Sites on Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer
Bando, H., Nakamura, Y., Taniguchi, H., Shiozawa, M., Yasui, H., Esaki, T., Kagawa, Y., Denda, T., Satoh, T., Yamazaki, K., et al. (2022) · JCO Precision Oncology · doi:10.1200/po.21.00535 · Cited by 111 · see citing works
Systemic treatment for metastatic colorectal cancer
Leowattana, W., Leowattana, P., & Leowattana, T. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i10.1569 · Cited by 111 · see citing works
Russo, A. D., Incorvaia, L., Re, M. D., Malapelle, U., Capoluongo, E., Gristina, V., Castiglia, M., Danesi, R., Fassan, M., Giuffrè, G., et al. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100164 · Cited by 105 · see citing works
Self-citationLiquid biopsies to monitor and direct cancer treatment in colorectal cancer
Mauri, G., Vitiello, P. P., Sogari, A., Crisafulli, G., Bianchi, A. S., Marsoni, S., Siena, S., & Bardelli, A. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01769-8 · Cited by 105 · see citing works
Treatment-driven tumour heterogeneity and drug resistance: Lessons from solid tumours
Crucitta, S., Cucchiara, F., Mathijssen, R. H. J., Mateo, J., Jager, A., Joosse, A., Passaro, A., Attili, I., Petrini, I., van Schaik, R. H., et al. (2022) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2022.102340 · Cited by 104 · see citing works
Self-citationThe Use of Circulating Tumor DNA to Monitor and Predict Response to Treatment in Colorectal Cancer
Reece, M. M., Saluja, H., Hollington, P., Karapetis, C. S., Vatandoust, S., Young, G. P., & Symonds, E. L. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.01118 · Cited by 92 · see citing works
Mauri, G., Pizzutilo, E. G., Amatu, A., Bencardino, K. B., Palmeri, L., Bonazzina, E. F., Tosi, F., Stella, G. C., Burrafato, G., Scaglione, F., et al. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.12.006 · Cited by 89 · see citing works
How we treat metastatic colorectal cancer
Falco, V. D., Napolitano, S., Roselló, S., Huerta, M., Cervantes, A. M. R., Ciardiello, F., & Troiani, T. (2019) · ESMO Open · doi:10.1136/esmoopen-2020-000813 · Cited by 90 · see citing works
Targeting the EGFR signalling pathway in metastatic colorectal cancer
Napolitano, S., Martini, G., Ciardiello, D., Tufo, S. D., Martinelli, E., Troiani, T., & Ciardiello, F. (2024) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(23)00479-x · Cited by 86 · see citing works
A novel protein RASON encoded by a lncRNA controls oncogenic RAS signaling in KRAS mutant cancers
Cheng, R., Li, F., Zhang, M., Xia, X., Wu, J., Gao, X., Zhou, H., Zhang, Z., Huang, N., Yang, X., et al. (2022) · Cell Research · doi:10.1038/s41422-022-00726-7 · Cited by 87 · see citing works
Yoshino, T., Cervantes, A. M. R., Bando, H., Martinelli, E., Oki, E., Xu, R., Mulansari, N. A., Babu, K. G., Lee, M. A., Tan, C., et al. (2023) · ESMO Open · doi:10.1016/j.esmoop.2023.101558 · Cited by 87 · see citing works
Parseghian, C. M., Sun, R., Woods, M. N., Napolitano, S., Lee, H. M., Alshenaifi, J. Y., Willis, J. A., Nunez, S., Raghav, K. P. S., Morris, V. K., et al. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.22.01423 · Cited by 84 · see citing works
Digestive cancers: mechanisms, therapeutics and management
Zhan, T., Betge, J., Schulte, N., Dreikhausen, L., Hirth, M., Li, M., Weidner, P., Leipertz, A., Teufel, A., & Ebert, M. P. A. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02097-4 · Cited by 85 · see citing works
The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer
Taı̈eb, J., Jung, A., Bianchi, A. S., Peeters, M., Seligmann, J. F., Zaanan, A., Burdon, P., Montagut, C. O., & Laurent‐Puig, P. (2019) · Drugs · doi:10.1007/s40265-019-01165-2 · Cited by 77 · see citing works
Jensen, L. H., Rogatto, S. R., Lindebjerg, J., Havelund, B. M., Abildgaard, C., do Canto, L. M., Vagn-Hansen, C., Dam, C., Rafaelsen, S. R., & Hansen, T. F. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02683-4 · Cited by 71 · see citing works
Cremolini, C., Chalabi, M., Élez, E., Fassan, M., Gelli, M., Goèré, D., Modest, D. P., Viladot, C. M., Osterlund, P. J., Ricke, J., et al. (2026) · Annals of Oncology · doi:10.1016/j.annonc.2026.03.005 · Cited by 78 · see citing works
Self-citationTopham, J. T., O'Callaghan, C. J., Feilotter, H., Kennecke, H. F., Lee, Y. S., Li, W., Banks, K. C., Quinn, K., Renouf, D. J., Jonker, D. J., et al. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.22.00364 · Cited by 70 · see citing works
Mitani, S., & Kawakami, H. (2020) · Cancers · doi:10.3390/cancers12020400 · Cited by 69 · see citing works
Yan, W., Qiu, L., Yang, M., Xu, A., Ma, M., Yuan, Q., Ma, X., Liang, W., Li, X., & Lu, Y. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216263 · Cited by 63 · see citing works
Gonzalez, N. S., Salvà, F., Ros, J., Baraibar, I., Rodríguez-Castells, M., García, A., Alcaráz, A., Vega, S., Bueno, S., Tabernero, J. M., et al. (2023) · Cancers · doi:10.3390/cancers15164020 · Cited by 64 · see citing works
Clinical application of circulating tumour DNA in colorectal cancer
Loft, M., To, Y. H., Gibbs, P., & Tie, J. (2023) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(23)00146-2 · Cited by 65 · see citing works
Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer
Ciardiello, D., Martinelli, E., Troiani, T., Mauri, G., Rossini, D., Martini, G., Napolitano, S., Famiglietti, V., Tufo, S. D., Masi, G., et al. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.5635 · Cited by 63 · see citing works
Self-citationCombined Treatment with Immunotherapy-Based Strategies for MSS Metastatic Colorectal Cancer
Baraibar, I., Mirallas, O., Gonzalez, N. S., Ros, J., Salvà, F., Tabernero, J. M., & Élez, E. (2021) · Cancers · doi:10.3390/cancers13246311 · Cited by 61 · see citing works
Napolitano, S., Falco, V. D., Martini, G., Ciardiello, D., Martinelli, E., Corte, C. M. D., Esposito, L., Famiglietti, V., Liello, A. D., Avallone, A., et al. (2023) · JAMA Oncology · doi:10.1001/jamaoncol.2023.0655 · Cited by 60 · see citing works
Self-citationUpdate in version 2021 of CSCO guidelines for colorectal cancer from version 2020
Dong, C., Ding, Y., Weng, S., Li, G., Huang, Y., Hu, H., Zhang, Z., Zhang, S., & Yuan, Y. (2021) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2021.03.02 · Cited by 59 · see citing works
Martini, G., Ciardiello, D., Vitiello, P. P., Napolitano, S., Cardone, C., Cuomo, A., Troiani, T., Ciardiello, F., & Martinelli, E. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102023 · Cited by 58 · see citing works
Immune Checkpoint Inhibitors in pMMR Metastatic Colorectal Cancer: A Tough Challenge
Marmorino, F., Boccaccino, A., Germani, M. M., Falcone, A., & Cremolini, C. (2020) · Cancers · doi:10.3390/cancers12082317 · Cited by 57 · see citing works
Self-citationResistance to targeted therapy in metastatic colorectal cancer: Current status and new developments
Tang, Y., Li, D., Duan, J.-Y., Sheng, L., & Wang, X. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i6.926 · Cited by 58 · see citing works
KRAS: A Druggable Target in Colon Cancer Patients
Negri, F., Bottarelli, L., de’Angelis, G. L., & Gnetti, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084120 · Cited by 55 · see citing works
Duffy, M. J., & Crown, J. P. (2022) · Clinical Chemistry · doi:10.1093/clinchem/hvac121 · Cited by 54 · see citing works
Klein‐Scory, S., Wahner, I., Maslova, M., Al‐Sewaidi, Y., Pohl, M., Mika, T., Ladigan, S., Schroers, R., & Baraniskin, A. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01115 · Cited by 52 · see citing works
Current and Emerging Biomarkers in Metastatic Colorectal Cancer
Lee, M. K. C., & Loree, J. M. (2019) · Current Oncology · doi:10.3747/co.26.5719 · Cited by 50 · see citing works
Molecular subtypes and the evolution of treatment management in metastatic colorectal cancer
Martini, G., Dienstmann, R., Ros, J., Baraibar, I., Cuadra‐Urteaga, J. L., Salvà, F., Ciardiello, D., Mulet-Margalef, N., Argilés, G., Tabernero, J. M., et al. (2020) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835920936089 · Cited by 52 · see citing works
Sunakawa, Y., Nakamura, M., Ishizaki, M., Kataoka, M., Satake, H., Kitazono, M., Yanagisawa, H., Kawamoto, Y., Kuramochi, H., Ohori, H., et al. (2020) · JCO Precision Oncology · doi:10.1200/po.20.00109 · Cited by 50 · see citing works
Güven, D. C., Şahin, T. K., Yildirim, H. Ç., Aktepe, O. H., Dızdar, Ö., & Yalçın, Ş. (2021) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2021.103528 · Cited by 50 · see citing works
Molecular Targets for the Treatment of Metastatic Colorectal Cancer
Cohen, R., Pudlarz, T., Delattre, J.-F., Colle, R., & André, T. (2020) · Cancers · doi:10.3390/cancers12092350 · Cited by 49 · see citing works
Masuishi, T., Tsuji, A., Kotaka, M., Nakamura, M., Kochi, M., Takagane, A., Shimada, K., Denda, T., Segawa, Y., Tanioka, H., et al. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-01042-w · Cited by 50 · see citing works
Anti‐angiogenesis in colorectal cancer therapy
Yang, Z., Zhang, X., Bai, X., Xi, X., Liu, W., & Zhong, W. (2024) · Cancer Science · doi:10.1111/cas.16063 · Cited by 50 · see citing works
Cetuximab as a Key Partner in Personalized Targeted Therapy for Metastatic Colorectal Cancer
Gonzalez, N. S., Ros, J., Baraibar, I., Salvà, F., Rodríguez-Castells, M., Alcaráz, A., García, A., Tabernero, J. M., & Élez, E. (2024) · Cancers · doi:10.3390/cancers16020412 · Cited by 47 · see citing works
Johnson, D., Chee, C. E., Wong, W., Lam, R. C. T., Tan, I. B. H., & Ma, B. B. Y. (2024) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2024.102700 · Cited by 48 · see citing works
Callesen, L. B., Hamfjord, J., Boysen, A. K., Pallisgaard, N., Guren, T. K., Kure, E. H., & Spindler, K. G. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01816-4 · Cited by 43 · see citing works
Liquid biopsies across the cancer care continuum
Landon, B. V., Annapragada, A. V., Niknafs, N., Velculescu, V. E., & Anagnostou, V. (2025) · Nature Medicine · doi:10.1038/s41591-025-04093-9 · Cited by 54 · see citing works
RAS as a positive predictive biomarker: focus on lung and colorectal cancer patients
Malapelle, U., Passiglia, F., Cremolini, C., Reale, M. L., Pepe, F., Pisapia, P., Avallone, A., Cortinovis, D. L., Stefano, A. D., Fassan, M., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.01.015 · Cited by 43 · see citing works
Self-citationYao, Y., Wang, Y., Chen, L., Tian, Z., Yang, G., Wang, R., Wang, C., Wu, Q., Wu, Y., Gao, J., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00908-0 · Cited by 41 · see citing works
Circulating Tumor DNA to Drive Treatment in Metastatic Colorectal Cancer
Patelli, G., Mauri, G., Tosi, F., Amatu, A., Bencardino, K. B., Bonazzina, E. F., Pizzutilo, E. G., Villa, F., Calvanese, G., Agostara, A. G., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-0079 · Cited by 41 · see citing works
Moati, É., Blons, H., Taly, V., Garlan, F., Renault, S., Pietrasz, D., Didelot, A., Garrigou, S., Saint, A., Pernot, S., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32657 · Cited by 41 · see citing works
Network approach in liquidomics landscape
Santini, D., Botticelli, A., Galvano, A., Iuliani, M., Incorvaia, L., Gristina, V., Taffon, C., Foderaro, S., Paccagnella, E., Simonetti, S., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02743-9 · Cited by 37 · see citing works
Self-citationUnveiling acquired resistance to anti-EGFR therapies in colorectal cancer: a long and winding road
Ríos-Hoyo, A., Monzonís, X., Vidal, J., Linares, J., & Montagut, C. O. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1398419 · Cited by 40 · see citing works
Ciracì, P., Studiale, V., Taravella, A., Antoniotti, C., & Cremolini, C. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00965-0 · Cited by 42 · see citing works
Self-citationRaghav, K. P. S., Ou, F., Venook, A. P., Innocenti, F., Sun, R., Lenz, H., & Kopetz, S. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.22.00365 · Cited by 39 · see citing works
Duffy, M. J., & Crown, J. P. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12010099 · Cited by 40 · see citing works
Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies
Turabi, K. S., Klute, K. A., & Radhakrishnan, P. (2024) · Cancers · doi:10.3390/cancers16132432 · Cited by 37 · see citing works
Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer
Lai, E., Liscia, N., Donisi, C., Mariani, S., Tolu, S., Pretta, A., Persano, M., Pinna, G., Balconi, F., Pireddu, A., et al. (2020) · Cancers · doi:10.3390/cancers12051214 · Cited by 37 · see citing works
Napolitano, S., Ciardiello, D., Falco, V. D., Martini, G., Martinelli, E., Corte, C. M. D., Esposito, L., Famiglietti, V., Liello, A. D., Avallone, A., et al. (2023) · International Journal of Cancer · doi:10.1002/ijc.34632 · Cited by 37 · see citing works
Hamid, M. A., Pammer, L. M., Oberparleiter, S., Günther, M., Amann, A., Gruber, R., Mair, A., Nocera, F. I., Ormanns, S., Zimmer, K., et al. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-00892-y · Cited by 40 · see citing works
Manca, P., Corallo, S., Lonardi, S., Fucà, G., Busico, A., Leone, A. G., Corti, F., Antoniotti, C., Procaccio, L., Smiroldo, V., et al. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01591-8 · Cited by 38 · see citing works
Self-citationJia, L.-L., Zhao, J.-X., Zhao, L., Tian, J., & Huang, G. (2022) · European Journal of Radiology · doi:10.1016/j.ejrad.2022.110640 · Cited by 36 · see citing works
Napolitano, S., Martini, G., Ciardiello, D., Di Maio, M., Normanno, N., Avallone, A., Martinelli, E., Maiello, E., Troiani, T., & Ciardiello, F. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.940523 · Cited by 35 · see citing works
Circulating tumor cells in colorectal cancer in the era of precision medicine
Hu, M., Wang, Z., Wu, Z., Ding, P., Pei, R., Wang, Q., & Xing, C. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02162-3 · Cited by 35 · see citing works
Boccaccino, A., Borelli, B., Intini, R., Antista, M., Bensi, M., Rossini, D., Passardi, A., Tamberi, S., Giampieri, R., Antonuzzo, L., et al. (2022) · ESMO Open · doi:10.1016/j.esmoop.2022.100506 · Cited by 36 · see citing works
Self-citationRecent Advances in Use of Topoisomerase Inhibitors in Combination Cancer Therapy
Wang, W., & Tse‐Dinh, Y. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190401113350 · Cited by 35 · see citing works
Circulating tumor DNA in colorectal cancer: opportunities and challenges.
Bi, F., Wang, Q., Dong, Q., Wang, Y., Zhang, L., & Zhang, J. (2020) · PubMed Central · Cited by 35 · see citing works
Patelli, G., Vaghi, C., Tosi, F., Mauri, G., Amatu, A., Massihnia, D., Ghezzi, S., Bonazzina, E. F., Bencardino, K. B., Cerea, G., et al. (2021) · Targeted Oncology · doi:10.1007/s11523-021-00795-5 · Cited by 35 · see citing works
Biomarker-Guided Anti-EGFR Rechallenge Therapy in Metastatic Colorectal Cancer
Ciardiello, D., Martini, G., Famiglietti, V., Napolitano, S., Falco, V. D., Troiani, T., Latiano, T. P., Ros, J., Élez, E., Vitiello, P. P., et al. (2021) · Cancers · doi:10.3390/cancers13081941 · Cited by 36 · see citing works
Osumi, H., Vecchione, L., Keilholz, U., Vollbrecht, C., Alig, A. H. S., von Einem, J. C., Stahler, A., Striefler, J. K., Kurreck, A., Kind, A. J., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.05.010 · Cited by 36 · see citing works
Xu, Y., Zhao, J., Ni, X., Wang, W., Hu, W., & Wu, C. (2021) · Epigenomics · doi:10.2217/epi-2021-0130 · Cited by 35 · see citing works
Battaglin, F., Puccini, A., Djaballah, S. A., & Lenz, H. (2019) · Cancer Management and Research · doi:10.2147/cmar.s186042 · Cited by 35 · see citing works
Current concepts of anti-EGFR targeting in metastatic colorectal cancer
Doleschal, B., Petzer, A., & Rumpold, H. F. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1048166 · Cited by 34 · see citing works
Nakajima, H., Kotani, D., Bando, H., Kato, T., Oki, E., Shinozaki, E., Sunakawa, Y., Yamazaki, K., Yuki, S., Nakamura, Y., et al. (2021) · BMC Cancer · doi:10.1186/s12885-021-08395-2 · Cited by 33 · see citing works
Current therapy of advanced colorectal cancer according to RAS/RAF mutational status
Lakatos, G., Köhne, C., & Bodoky, G. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09913-7 · Cited by 30 · see citing works
Kim, S. Y., & Kim, T. W. (2020) · ESMO Open · doi:10.1136/esmoopen-2019-000634 · Cited by 31 · see citing works
Ozawa, S., Miura, T., Terashima, J., & Habano, W. (2021) · Cancer Drug Resistance · doi:10.20517/cdr.2021.82 · Cited by 30 · see citing works
Loree, J. M., Dowers, A., Tu, D., Jonker, D. J., Edelstein, D. L., Quinn, H., Holtrup, F., Price, T. J., Zalcberg, J. R., Moore, M. J., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2710 · Cited by 29 · see citing works
Xu, X., Ai, L., Hu, K., Liang, L., Lv, M., Wang, Y., Cui, Y., Li, W., Li, Q., Yu, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51536-x · Cited by 30 · see citing works
- Authors
- Cremolini, C., Rossini, D., Dell’Aquila, E., Lonardi, S., Conca, E., Del Re, M., Busico, A., Pietrantonio, F., Danesi, R., Aprile, G., Tamburini, E., Barone, C., Masi, G., Pantano, F., Pucci, F., Corsi, D. C., Pella, N., Bergamo, F., Rofi, E., Barbara, C., Falcone, A., & Santini, D.
- Affiliations
- University of Pisa (IT)
- Università Campus Bio-Medico (IT)
- Istituto Oncologico Veneto (IT)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, Pisa, Italy
- University of Udine (IT)
- Ospedale Infermi di Rimini (IT)
- Università Cattolica del Sacro Cuore (IT)
- Ospedale di Parma (IT)
- Fatebenefratelli Hospital (IT)
- Medical Oncology Unit, Presidio Ospedaliero Felice Lotti, Pontedera, Italy
- Corresponding author
- Falcone, Alfredo
- ORCID
- Venue
- JAMA Oncology
- Publisher
- American Medical Association (AMA)
- Published
- 2019-03-01
- Volume
- 5
- Issue
- 3
- Pages
- 343
- ISSN
- 2374-2437 (ISSN-L)
- PMC
- PMC6439839
- OpenAlex
- W2901178367
- Cited by
- 424
- References
- 38
- Citations by year
- 2026: 36 · 2025: 48 · 2024: 75 · 2023: 66 · 2022: 72 · 2021: 61 · 2020: 47 · 2019: 18 · 2018: 1
- FWCI
- 11.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Amgen
- Eli Lilly and Company
- Sanofi
- Celgene
- F. Hoffmann-La Roche
- Merck KGaA
- Eisai
- Università Cattolica del Sacro Cuore
- Servier
- Ipsen
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- metastatic colorectal cancer, cetuximab, irinotecan, drug rechallenge, RAS wild-type, BRAF wild-type, acquired resistance, anti-EGFR therapy, circulating tumor DNA, liquid biopsy, third-line therapy, oxaliplatin, bevacizumab, RAS mutations, progression-free survival, overall survival, response rate, disease control rate, predictive biomarkers
- MeSH terms
- Cetuximab, Irinotecan, Progression-Free Survival, Aged, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Italy, Male, Middle Aged, Prospective Studies, Genes, ras, Risk Factors, Time Factors, Biomarkers, Tumor, Colorectal Neoplasms, Disease Progression, Drug Resistance, Neoplasm, Proto-Oncogene Proteins B-raf
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