The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial
Open accessAbstract
Importance: Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. Objective: To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer. Design, Setting, and Participants: Patients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015. Interventions: Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient. Main Outcomes and Measures: The primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response. Results: Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0-110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77-1.01; P = .08). The median progression-free survival was 10.5 months in the cetuximab-chemotherapy group and 10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95% CI, 0.84-1.08; P = .45). Response rates were not significantly different, 59.6% vs 55.2% for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0%-9.0%, P = .13). Conclusions and Relevance: Among patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment. Trial Registration: clinicaltrials.gov identifier: NCT00265850.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Also, patients with metastatic colorectal cancer and related intestinal malignancies tend to receive similar treatments and live for many months with relatively stable health (median overall survival >2 years) [44], facilitating study completion and potentially derivation of durable benefit from the intervention.”
From Being present: A single-arm feasibility study of audio-based mindfulness meditation for colorectal cancer patients and caregivers (2018) · cites this paper as [44]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Although a higher percentage of men enrolled compared to most prior mindfulness interventions for integrative cancer care [34], the evaluable study sample included a greater proportion of younger (age <50), female, White and Latino or Hispanic patients relative to the underlying population [44, 53].”
From Being present: A single-arm feasibility study of audio-based mindfulness meditation for colorectal cancer patients and caregivers (2018) · cites this paper as [44]
Experimental — accuracy not yet measuredIn the citing paper
“This trial demonstrated that patients in the cetuximab plus chemotherapy group had slightly higher overall survival versus patients in the bevacizumab plus chemotherapy group (30.0 months versus 29.0 months).”
From Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer (2024) · cites this paper as [65]
In the citing paper
“Similar to the FIRE-3 trial, median progression-free survival and response rates were similar between groups.”
From Update on Targeted Therapy and Immunotherapy for Metastatic Colorectal Cancer (2024) · cites this paper as [65]
In the citing paper
“Similarly, the CALGB/SWOG 80405 trial showed that both cetuximab and bevacizumab provided comparable outcomes when combined with chemotherapy in the overall population, but the benefit of anti-EGFR therapy was again limited to RAS wild-type tumors [21].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [21]
In the citing paper
“however, it must be noted here that this pooled analysis also included patients who had received a nonstandard treatment regimen, including FUFIRI, FUFOX, and mIROX as induction chemotherapies and bevacizumab monotherapy or observation alone as maintenance therapies in clinical trials [22,23].”
From The Prognostic Impact of KRAS G12C Mutation in Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Observational Study (2021) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660
Toxicity and response criteria of the Eastern Cooperative Oncology Group
Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., Mcfadden, E. T., & Carbone, P. P. (1982) · American Journal of Clinical Oncology · doi:10.1097/00000421-198212000-00014 · Cited by 11,686
Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer
Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W., Berlin, J., Baron, A., Griffing, S., Holmgren, E., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032691 · Cited by 10,968 · cited 2×
“dence indicated that cetuximab activity was unrelated to tumor expression of EGFR.(8) Bevacizumab, a humanized”
BackgroundThe consensus molecular subtypes of colorectal cancer
Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., et al. (2015) · Nature Medicine · doi:10.1038/nm.3967 · Cited by 5,170
Cunningham, D., Humblet, Y., Siena, S., Khayat, D., Bleiberg, H., Santoro, A., Bets, D., Mueser, M., Harstrick, A., Verslype, C., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa033025 · Cited by 5,035
de Gramont, A., Figer, A., Seymour, M., Homerin, M., Hmissi, A., Cassidy, J., Boni, C., Cortes-Funes, H., Cervantes, A., Freyer, G., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.16.2938 · Cited by 3,815 · cited 1×
“a The 0-to-5 coded scale describing patient daily level of functioning from fully active (0) to completely disabled (4); dead (5).”
BackgroundDouillard, J., Cunningham, D., Roth, A., Navarro, M., James, R., Karasek, P., Jandik, P., Iveson, T., Carmichael, J., Alakl, M., et al. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02034-1 · Cited by 3,256 · cited 4×
“Results are reported for (1) the primary 2-group comparison between cetuximab and bevacizumab; (2) the comparison of cetuximab vs bevacizumab in an expanded RAS subset described above; and (3) the chemotherapy subgroups.”
MethodInfluentialSaltz, L. B., Clarke, S., Díaz-Rubio, E., Scheithauer, W., Figer, A., Wong, R., Koski, S., Lichinitser, M., Yang, T.-S., Rivera, F., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.9930 · Cited by 2,955
Tournigand, 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
Heinemann, V., von Weikersthal, L. F., Decker, T., Kiani, A., Vehling-Kaiser, U., Al-Batran, S.-E., Heintges, T., Lerchenmüller, C., Kahl, C., Seipelt, G., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70330-4 · Cited by 1,740
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–500 of 900
Sakamoto, K., Beppu, T., Honda, G., Kotake, K., Yamamoto, M., Takahashi, K., Endo, I., Hasegawa, K., Itabashi, M., Hashiguchi, Y., et al. (2022) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.1252 · Cited by 10
Höchster, H. S., Catalano, P. J., Weitz, M., Mitchell, E., Cohen, D. J., O'Dwyer, P. J., Faller, B. A., Kortmansky, J. S., O’Hara, M. H., Kricher, S. M., et al. (2024) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djae114 · Cited by 10
Self-citationGraham, C. N., Christodoulopoulou, A., Knox, H. N., Sabatelli, L., Hechmati, G., Garawin, T., & Strickler, J. H. (2018) · Journal of Medical Economics · doi:10.1080/13696998.2018.1510409 · Cited by 10
Asimakopoulou, N., Souglakos, J., Kentepozidis, N. K., Karampeazis, A., Kotsakis, A. P., Ziras, N., Makrantonakis, P., Prinarakis, E., Vamvakas, L. N., & Georgoulias, V. (2018) · Journal of Geriatric Oncology · doi:10.1016/j.jgo.2018.08.002 · Cited by 10
Liver-Directed and Systemic Therapies for Colorectal Cancer Liver Metastases
Kemeny, N. E., Kurilova, I., Li, J., Camacho, J. C., & Sofocleous, C. T. (2019) · CardioVascular and Interventional Radiology · doi:10.1007/s00270-019-02284-9 · Cited by 10
Poel, D., Gootjes, E. C., Bakkerus, L., Trypsteen, W., Dekker, H., van der Vliet, H. J., van Grieken, N. C. T., Verhoef, C. K., Buffart, T. E., & Verheul, H. M. W. (2020) · Cancer Medicine · doi:10.1002/cam4.3371 · Cited by 10
Guercio, B. J., Zhang, S., Ou, F., Venook, A. P., Niedzwiecki, D., Lenz, H., Innocenti, F., Pollak, M., Nixon, A. B., Mullen, B. C., et al. (2020) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkaa074 · Cited by 10
“Participants did not receive any systemic therapy for mCRC prior to trial enrollment (16).”
Self-citationLiang, L., Liu, M., Sun, X., Yuan, Y., Peng, K., Rashid, K., Yu, Y., Cui, Y., Chen, Y., & Liu, T. (2021) · Cancer Cell International · doi:10.1186/s12935-021-01829-8 · Cited by 10
Zhou, Y., Long, Y., Chen, Y., Liu, J., Pu, D., Huang, J., Bi, F., Li, Q., Gou, H., & Qiu, M. (2021) · Cancer Medicine · doi:10.1002/cam4.3876 · Cited by 10
Occurence of RAS reversion in metastatic colorectal cancer patients treated with bevacizumab
Epistolio, S., Cefalì, M., Spina, P., Molinari, F., Movilia, A., Cergnul, M., Mazzucchelli, L., Dosso, S. D., Frattini, M., & Saletti, P. (2021) · Oncotarget · doi:10.18632/oncotarget.27965 · Cited by 10
Lukoševičius, R., Juzėnas, S., Šaltenienė, V., Kulokiene, U., Arstikyte, J., Hemmrich‐Stanisak, G., Franke, A., Link, A., Ruzgys, P., Šatkauskas, S., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042107 · Cited by 10
“, anti-VEGF and anti-EGFR monoclonal antibodies [5]) and patient stratification strategies [6].”
BackgroundJiang, W., Yu, Q., Ning, R., Zhao, W., & Wei, C. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s168695 · Cited by 10
“However, the mFOLFOX6 regimen was only administered in the PEAK study(14,15) and to the majority of patients (73%) in CALGB/ SWOG 80405.(11) Therefore, the possibility that the survival benefits of EGFR inhibitors in the entire patient population are derived from the mFOLFOX6 regimen setting should be further explored.”
MethodComparing the use of Arabic decision aid to usual care
Al-Sagheir, A. I., Al-Rowais, N. A., Alkhudhair, B. K., Alyousefi, N. A., Sagheir, A. I. A., Ali, A., & AlMakoshi, A. (2020) · Saudi Medical Journal · doi:10.15537/smj.2020.5.25064 · Cited by 9
Tsai, H., Lin, C., Sung, Y.-C., Chen, S., Chen, L., Jiang, J., & Wang, J. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02366-z · Cited by 9
Gasdermin D regulates the activation of EGFR in colorectal cancer
Li, Y., Chen, J., Liang, H., Du, Q., Shen, J., & Wang, X. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05984-0 · Cited by 9
Taniguchi, H., Uehara, K., Ishikawa, T., Okochi, O., Akazawa, N., Okuda, H., Hasegawa, H., Shiozawa, M., Kataoka, M., Satake, H., et al. (2025) · Cancers · doi:10.3390/cancers17030399 · Cited by 11
“Previous RCTs have reported mixed results; the FIRE-3 trial showed better OS with EGFR combination therapy, while the CALGB80405 trial found no difference [46,47].”
Guo, Z., He, L., Wang, W., Tian, S., & Lin, R. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217643 · Cited by 9
Huang, S., Lin, C., Teng, H., Lin, H., Chang, S., Lan, Y., Wang, H., Yang, S.-H., Chen, W., & Jiang, J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.808808 · Cited by 9
Policies and Practices to Address Cancer’s Long-Term Adverse Consequences
Bradley, C. J., Kitchen, S., Bhatia, S., Bynum, J., Darien, G., Lichtenfeld, J. L., Oyer, R. A., Shulman, L. N., & Sheldon, L. K. (2022) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djac086 · Cited by 15
Matsumoto, T., Ikoma, T., Yamamura, S., Miura, K., Tsuduki, T., Watanabe, T., Nagai, H., Takatani, M., & Yasui, H. (2023) · Scientific Reports · doi:10.1038/s41598-023-29706-6 · Cited by 9
Otsu, S., & Hironaka, S. (2023) · Cancers · doi:10.3390/cancers15184564 · Cited by 9
“Unresectable colorectal cancer is difficult to cure, but advances in drug therapy have led to a median survival of over 30 months [3,4].”
BackgroundBüchler, T., Chloupková, R., Poprach, A., Fiala, O., Kišš, I., Kopečková, K., Dušek, L., Veškrňová, V., Slavicek, L., Kohoutek, M., et al. (2018) · Cancer Management and Research · doi:10.2147/cmar.s183093 · Cited by 9
“No differences in PFS or ORR were reported, and OS was also similar between patients receiving VEGFi and EGFRi therapy, contrasting with results of the FIRE-3 and the PEAK studies.(3) Three meta-analyses of these randomized studies have been carried out, all showing superior OS in patients who start with EGFRi as oppo…”
ResultDevaux, M., Gérard, L., Richard, C., Bengrine-Lefèvre, L., Vincent, J., Schmitt, A., & Ghiringhelli, F. (2019) · World Journal of Clinical Oncology · doi:10.5306/wjco.v10.i2.75 · Cited by 10
Raimondi, A., Corallo, S., Lonardi, S., Antoniotti, C., Rimassa, L., Amatu, A., Tampellini, M., Racca, P., Murialdo, R., Clavarezza, M., et al. (2021) · Supportive Care in Cancer · doi:10.1007/s00520-020-05972-2 · Cited by 9
Li, S., Dong, D., Geng, J., Zhu, X., Chen, S., Zhang, Y., Wang, H., Zhou, S., Wu, H., Cai, Y., et al. (2021) · Asia-Pacific Journal of Clinical Oncology · doi:10.1111/ajco.13557 · Cited by 9
Gallois, C., Hafliger, É., Auclin, É., Perret, A., Coutzac, C., Turpin, A., Pellat, A., Randrian, V., Basile, D., Faroux, R., et al. (2021) · Digestive and Liver Disease · doi:10.1016/j.dld.2021.08.009 · Cited by 9
Jin, H., Amonkar, M. M., Aguiar‐Ibáñez, R., Thosar, M., Chase, M., & Keeping, S. (2022) · Future Oncology · doi:10.2217/fon-2021-1633 · Cited by 9
Randrian, V., Pernot, S., Malicot, K. L., Catena, V., Baumgaertner, I., Tacher, V., Forestier, J., Hautefeuille, V., Tabouret-Viaud, C., Gagnaire, A., et al. (2022) · Digestive and Liver Disease · doi:10.1016/j.dld.2022.04.024 · Cited by 9
“In the first-line setting the recommended treatment for mCRC is Oxaliplatin- and/or Irinotecan-based chemotherapy associated with targeted therapy according to KRAS status [2,3].”
BackgroundZhang, C., Liu, L., Lv, Y., Li, J., Cao, C., Lu, J., Wang, S., Du, B., & Yang, X. (2022) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2022.2147512 · Cited by 9
“Six studies described the methods of allocation concealment [20,22,23,33,36,39,40].”
BackgroundMethodResultInfluentialFanotto, V., Salani, F., Vivaldi, C., Scartozzi, M., Ribero, D., Puzzoni, M., Montagnani, F., Leone, F., Vasile, E., Bencivenga, M., et al. (2023) · Cancers · doi:10.3390/cancers15030900 · Cited by 9
Albin, N., Leer, A. M., & Sakhri, L. (2018) · Bulletin du Cancer · doi:10.1016/j.bulcan.2018.01.009 · Cited by 8
Decoding Metastatic Colorectal Cancer to Improve Clinical Decision Making
Stebbing, J., & Wasan, H. S. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.19.01185 · Cited by 9
Cancers colorectaux avec mutation V600E de BRAF : où en sommes-nous ?
Lièvre, A., de la Fouchardière, C., Samalin, E., Benoist, S., Phelip, J., André, T., & Lledo, G. (2020) · Bulletin du Cancer · doi:10.1016/j.bulcan.2020.04.017 · Cited by 9
Internò, V., Tucci, M., Pezzicoli, G., Silvestris, F., Porta, C., & Mannavola, F. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.581130 · Cited by 9
Margalit, O., Harmsen, W. S., Shacham‐Shmueli, E., Voss, M. M., Boursi, B., Wagner, D., Cohen, R., Olswold, C. L., Saltz, L. B., Goldstein, D. A., et al. (2022) · European Journal of Cancer · doi:10.1016/j.ejca.2022.10.022 · Cited by 8
Self-citationYan, H., Liu, J., Zhang, Y., Chen, S., Xu, J., Gao, D., Li, H., Fang, X., Wang, Y., Wang, H., et al. (2024) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo-24-180 · Cited by 8
“In recent years, the combination of radiation therapy, targeted therapy, and immunotherapy has dramatically improved the median overall survival (mOS) of mCRC patients, which can reach 30 months (4).”
Li, B., Yang, W., Liu, N., Bi, D., Yang, T., Wu, G., & Sun, Y. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02885-3 · Cited by 9
Matsuhashi, N., Takahashi, T., Matsui, S., Tanahashi, T., Imai, H., Tanaka, Y., Yamaguchi, K., & Yoshida, K. (2018) · International Journal of Oncology · doi:10.3892/ijo.2018.4322 · Cited by 8
“…response in unresectable-type and borderline resectable-type cancer with liver metastasis treated with anti-EGFR monoclonal antibodies (10), as the CALGB/SWOG 80405 trial showed no superiority in overall survival (OS) between anti-VEGF monoclonal antibodies and anti-EGFR monoclonal antibodies (11).”
Diaz-Mercedes, S., Archilla, I., Camps, J., de Lacy, A., Gorostiaga, Í., Momblan, D. N. D. M., Ibarzábal, A., Maurel, J., Chic, N., Bombí, J. A., et al. (2019) · Applied Health Economics and Health Policy · doi:10.1007/s40258-019-00482-7 · Cited by 8
SPOCK1 silencing decreases 5-FU resistance through PRRX1 in colorectal cancer
Qu, Y.-L., Liu, X., Zhao, S., & Zhai, X. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.153895 · Cited by 8
Cui, Y., & Guo, Y. (2022) · International Journal of Clinical Pharmacy · doi:10.1007/s11096-022-01415-6 · Cited by 8
Iyer, P., Deng, M., Handorf, E. A., Nakhoda, S., & Dotan, E. (2022) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkac065 · Cited by 8
“The gradual adoption of these guidelines may be because of the short time interval between the publication of the above data in June 2017 and the end of our data collection in 2018 (52).”
BackgroundBoccaccino, A., Rossini, D., Raimondi, A., Carullo, M., Lonardi, S., Morano, F., Santini, D., Tomasello, G., Niger, M., Zaniboni, A., et al. (2023) · European Journal of Cancer · doi:10.1016/j.ejca.2023.05.001 · Cited by 8
Yasui, H., Okita, Y., Nakamura, M., Sagawa, T., Watanabe, T., Kataoka, K., Manaka, D., Shiraishi, K., Akazawa, N., Okuno, T., et al. (2023) · ESMO Open · doi:10.1016/j.esmoop.2023.101636 · Cited by 9
Wesdorp, N. J., Zeeuw, M. J., van der Meulen, D., Erve, I. V. ’., Bodalal, Z., Roor, J., van Waesberghe, J. H., Moos, S. I., van den Bergh, J., Nota, I., et al. (2023) · Cancers · doi:10.3390/cancers15235648 · Cited by 9
Burge, M., Semira, C., Lee, B., Lee, M., Kosmider, S., Wong, R., Shapiro, J. D., Ma, B. B. Y., Dean, A. P., Zimet, A. S., et al. (2018) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2018.05.009 · Cited by 8
Marques, R. P., Heudtlass, P., Pais, H. L., Quintela, A., & Martins, A. P. (2019) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-019-02924-0 · Cited by 8
“Conversely, we would expect a change in the body image scale, driven by the incidence of skin-related toxicities that frequently occur in cetuximab-treated patients (Heinemann et al. 2014; Venook et al. 2017).”
BackgroundInfluentialOptimizing Biologic Sequencing in Metastatic Colorectal Cancer: First Line and Beyond
Jin, Z., & Hubbard, J. M. (2019) · Current Oncology · doi:10.3747/co.26.5589 · Cited by 8
Kasper, S., Meiler, J., Knipp, H., Höhler, T., Reimer, P., Steinmetz, T., Berger, W., Linden, G., Reis, H., Markus, P. M., et al. (2020) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2020.03.003 · Cited by 8
Liu, S., Jiang, C., Yang, L., Huang, J., Peng, R., Wang, X., He, W., Bai, L., Zhou, Y., Zhang, B., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-69230-5 · Cited by 9
Xie, X., Zhang, J., Hu, H., Cai, Y., Wu, Z., Ling, J., Li, W., & Deng, Y. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01447-2 · Cited by 9
Bang, Y. H., Kim, J. E., Lee, J. S., Kim, S. Y., Kim, K., Kim, T. W., & Hong, Y. S. (2021) · Scientific Reports · doi:10.1038/s41598-021-86482-x · Cited by 9
Nishizawa, Y., Haraguchi, N., Kim, H., Ide, Y., Nakata, K., Okamura, S., Kudo, T., Satoh, T., Uemura, M., Matsuda, C., et al. (2021) · BMC Cancer · doi:10.1186/s12885-021-08690-y · Cited by 8
Wang, C., Yang, M., Gu, X., & Gu, Y. (2021) · Bioengineered · doi:10.1080/21655979.2021.1974655 · Cited by 8
“For mCRC cases, the application of CTX combined with conventional chemotherapy has been used as a typical therapeutic method to reduce progression risks and appears to be more active than cytotoxic chemotherapies alone [12].”
MethodBoisteau, É., Lespagnol, A., de Tayrac, M., Corre, S., Perrot, A., Rioux-Leclercq, N. C., Martin‐Lannerée, S., Artru, P., Chalabreysse, P., Poureau, P.-G., et al. (2022) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2022.101888 · Cited by 8
Alfonso, P. G., Lièvre, A., Loupakis, F., Tadmouri, A., Khan, S., Barcena, L., & Stintzing, S. (2022) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2022.103646 · Cited by 8
Brown, J. C., Brighton, E., Campbell, N., McCleary, N. J., Abrams, T. A., Cleary, J. M., Enzinger, P. C., Ng, K., Rubinson, D. A., Wolpin, B. M., et al. (2022) · BMJ Open Sport & Exercise Medicine · doi:10.1136/bmjsem-2022-001353 · Cited by 8
Self-citationBlarigan, E. L. V., Ma, C., Ou, F., Bainter, T. M., Venook, A. P., Ng, K., Niedzwiecki, D., Giovannucci, E. L., Lenz, H., Polite, B. N., et al. (2022) · International Journal of Cancer · doi:10.1002/ijc.34230 · Cited by 9
“BMI (kg/m(2)), median (IQR) 27 (24, 32) 27 (24, 32) 27 (24, 31) 28 (25, 32) Smoking status”
MethodInfluentialSelf-citationAkbulut, S., Hargura, A. S., Garzali, I. U., Aloun, A., & Çolak, C. (2022) · World Journal of Clinical Cases · doi:10.12998/wjcc.v10.i26.9228 · Cited by 8
Current and emerging anti-angiogenic therapies in gastrointestinal and hepatobiliary cancers
Gonzalez, N. S., Castet, F., Élez, E., Macarulla, T. M., & Tabernero, J. M. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1021772 · Cited by 9
Raunkilde, L., Hansen, T. F., Havelund, B. M., Thomsen, C. B., Rafaelsen, S. R., Lindebjerg, J., & Jensen, L. H. (2023) · Acta Oncologica · doi:10.1080/0284186x.2023.2249225 · Cited by 8
McGregor, M., & Price, T. J. (2018) · Future Oncology · doi:10.2217/fon-2017-0711 · Cited by 8
First‐line therapy for metastatic colorectal cancer: Current perspectives and future directions
Burge, M., Price, T. J., & Karapetis, C. S. (2019) · Asia-Pacific Journal of Clinical Oncology · doi:10.1111/ajco.13119 · Cited by 8
Gootjes, E. C., Kraan, J., Buffart, T. E., Bakkerus, L., Zonderhuis, B. M., Verhoef, C. K., Verheul, H. M. W., & Sleijfer, S. (2020) · Cells · doi:10.3390/cells9010124 · Cited by 8
Karimi, M., Wang, C., Bahadini, B., Hajjar, G., & Fakih, M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9061687 · Cited by 8
“For this group of patients, the addition of anti-EGFR therapy to combination chemotherapy in the first-line setting is better than bevacizumab according to subgroup analyses from two large randomized trials [10,11].”
MethodCarcinoma of the Colon and Rectum
Suzuki, Y., Tyler, D. S., & Phatak, U. R. (2022) · Holland‐Frei Cancer Medicine · doi:10.1002/9781119000822.hfcm144 · Cited by 8
Yazdani, A., Lenz, H., Pillonetto, G., Méndez-Giráldez, R., Yazdani, A., Sanoff, H. K., Hadi, R., Samiei, E., Venook, A. P., Ratain, M. J., et al. (2025) · Communications Medicine · doi:10.1038/s43856-024-00728-z · Cited by 11
Self-citationJin, Z., Li, Y., Hao, Y., Wang, M., Wang, C., Du, S., Zeng, W., & Zong, Z. (2025) · International Journal of Oncology · doi:10.3892/ijo.2025.5728 · Cited by 8
“The results of several large clinical studies comparing the combination regimens of bevacizumab and cetuximab with FOLFOX/FOLFIRI were fairly consis‑ tent, with no significant difference in response rate or PFS between the two groups and prolonged OS in the cetuximab group (168,169).”
Zhang, L., Shen, H., & Zhang, N. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1581015 · Cited by 11
Yang, E.-W., Waldrup, B., & Velazquez-Villarreal, E. I. (2025) · Biomedicines · doi:10.3390/biomedicines13081835 · Cited by 7
Strelez, C., Battaglin, F., Perez, R. G., Yang, Y., Cherry, C., Millstein, J., Yoon, A. Y., Chlystek, J. S., Canfield, E. J., Haliday, B., et al. (2025) · Oncogene · doi:10.1038/s41388-025-03546-2 · Cited by 7
Self-citationLiang, Y., Chen, K., & Shao, Y. (2023) · Cancer Medicine · doi:10.1002/cam4.6196 · Cited by 7
Bonilla, C., Montenegro, P., O’Connor, J. M., Hernando, O., Aranda, E., Pinto-Llerena, J., Llontop, A., Escobar, J. G., Romero, M. D. C. D., Bautista-Hernández, Y., et al. (2023) · Cancers · doi:10.3390/cancers15174373 · Cited by 8
“Identification of a driver gene mutation or other biomarkers can lead to specific targeted therapies, resulting in precision and personalized medicine that can improve the clinical outcomes of these patients [2].”
BackgroundRodríguez-Castells, M., Baraibar, I., Ros, J., Gonzalez, N. S., Salvà, F., García, A., Alcaráz, A., Tabernero, J. M., & Élez, E. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1272561 · Cited by 8
Huang, Z., Li, C., Huang, Y., Liang, W., & Tao, H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1425596 · Cited by 7
Coupez, D., Hulo, P., Touchefeu, Y., Denis, M. G., & Bennouna, J. (2021) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2021.1967318 · Cited by 8
Chen, R., Liu, Y., Hu, S., Yin, Z., Nie, Y., Xu, H., Zhong, Y., Zhu, Y., Liang, X., & Xu, H. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-77 · Cited by 7
“Previous studies have demonstrated that fluorouracil-based chemotherapy in combination with bevacizumab significantly improves progression-free survival (PFS) and overall survival (OS) in the first- and second-line treatment of mCRC (4,9).”
BackgroundRashad, N., Abdulla, M., Farouk, M., Elkerm, Y., Salem, S. E., Yehia, M., Saad, A. S., Aziz, A. H. A., Refaat, G., Awad, I., et al. (2022) · Cancer Management and Research · doi:10.2147/cmar.s340030 · Cited by 7
Su, Y., Wu, C., Su, C., Hsieh, M., Cheng, C., & Yang, Y. K. (2022) · Cancers · doi:10.3390/cancers14092118 · Cited by 7
Erol, C., Sendur, M. A. N., Bilgetekin, İ., Garbioglu, D. B., Hamdard, J., Akbaş, S., Hızal, M., Arslan, Ç., Sevinç, A., Küçükarda, A., et al. (2022) · Journal of Cancer Research and Therapeutics · doi:10.4103/jcrt.jcrt_1104_21 · Cited by 7
Cheng, P., Chen, H., Huang, F., Li, J., Liu, H., Zheng, Z., & Lu, Z. (2022) · Scientific Reports · doi:10.1038/s41598-022-18258-w · Cited by 7
Gbolahan, O. B., Hashemi‐Sadraei, N., Suri, Y., Williams, G. R., Ramachandran, R., Kim, Y. I., Paluri, R. K., Outlaw, D. A., El‐Rayes, B. F., & Nabell, L. (2022) · Cancer Medicine · doi:10.1002/cam4.5133 · Cited by 7
Sommerhäuser, G., Kurreck, A., Beck, A., Fehrenbach, U., Karthaus, M., Fruehauf, S., Graeven, U., Mueller, L., König, A. O., von Weikersthal, L. F., et al. (2022) · European Journal of Cancer · doi:10.1016/j.ejca.2022.09.011 · Cited by 7
Poad, H., Khan, S., Wheaton, L., Thomas, A., Sweeting, M. J., & Bujkiewicz, S. (2022) · Cancers · doi:10.3390/cancers14215391 · Cited by 7
Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study
Pericay, C., Montés, A. F., Alonso-Orduña, V., Macías, I., Asensio, E., Salas, N. R., Torres, E., Lavín, D. C., Rodríguez-Alonso, R. M., Falcó, E., et al. (2023) · Cancers · doi:10.3390/cancers15184603 · Cited by 7
“Finally, the randomized CALGB 80,405 study, where the choice of first-line chemotherapy was not prespecified, found that 73.4% of patients received oxaliplatin-based chemotherapy and 26.6% received irinotecan-based chemotherapy as first-line treatment [26].”
BackgroundInfluentialShin, Y. J., Jo, E. H., Oh, Y., Kim, D. S., Hyun, S., Yu, A.-R., Hong, H. K., & Cho, Y. B. (2023) · Cancers · doi:10.3390/cancers15235531 · Cited by 7
“The first-line chemotherapy for CRC is a critical decision that determines the overall survival (OS) [38,39].”
BackgroundSato, Y., Hirakawa, M., Ohnuma, H., Takahashi, M., Okamoto, T., Okamoto, K., Miyamoto, H., Muguruma, N., Furuhata, T., Takemasa, I., et al. (2017) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-017-3458-7 · Cited by 7
Qiu, T., Chen, W., Li, P., Sun, J., Gu, Y., & Chen, X. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s149110 · Cited by 7
Wang, J., Wu, H., Zhu, M., & Zhou, R. (2018) · Pathology & Oncology Research · doi:10.1007/s12253-017-0365-5 · Cited by 7
“Therefore, a final total of four RCTs [14–17] determine the impact of anti-EGFR and anti-VEGF therapies in the first-line therapy for mCRC.”
MethodResultInfluentialLau‐Min, K. S., Prakash, P., Jo, E., Thrift, A. P., Hilsenbeck, S. G., & Musher, B. (2020) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2019.09.002 · Cited by 7
Liu, C., Li, Y., Qin, X., Yang, Z., Luo, J., Zhang, J., Gray, B. D., Pak, K. Y., Xu, X., Cheng, J., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.109947 · Cited by 7
Kurreck, A., Heinemann, V., von Weikersthal, L. F., Decker, T. W., Kaiser, F., Uhlig, J., Schenk, M., Freiberg‐Richter, J., Peuser, B., Denzlinger, C., et al. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2020.06.010 · Cited by 7
Yuan, M., Wang, Z., Zhao, Y., Feng, T., Lv, W., & Zhong, H. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.632076 · Cited by 7
“The use of chemotherapy regimens based on these drugs combined with molecular targeted drugs including cetuximab and bevacizumab to treat mCRC has already become a clinical consensus at the first-line treatment (Heinemann et al., 2014; Venook et al., 2017).”
BackgroundNgassa, H. C., Elmenawi, K. A., Anil, V., Gosal, H., Kaur, H., & Mohammed, L. (2021) · Cureus · doi:10.7759/cureus.17712 · Cited by 7
“CRC is among the principal reasons people die of cancer worldwide, the second most common cause for cancer-linked death in North America and Europe [1,9].”
BackgroundRong, X., Liu, H., Yu, H., Zhao, J. G., Wang, J., & Wang, Y. (2022) · Investigational New Drugs · doi:10.1007/s10637-021-01205-3 · Cited by 7
Tanaka, T., Suzuki, H., Ushijima, T., Nagasu, S., Akagi, Y., Kawaguchi, T., & Miwa, K. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.947013 · Cited by 7
Sutherland, R. L., Boyne, D. J., Brenner, D. R., & Cheung, W. Y. (2023) · Cancers · doi:10.3390/cancers15245748 · Cited by 7
Clinical Progress of Fruquintinib in Colorectal Cancer: An Overview
Xie, Y., Tang, S., Qin, Z., & Yang, C. (2025) · Pharmaceuticals · doi:10.3390/ph18020280 · Cited by 6
“The standard first-line regimen usually consists of FOLFOX (oxaliplatin in combination with fluorouracil and calcium folinic acid) or FOLFIRI (irinotecan in combination with fluorouracil and calcium folinic acid) alongside targeted therapeutic agents like bevacizumab or cetuximab [4,5].”
Colorectal cancer treatment commentary review
Önder, A. H., & Çatlı, M. M. (2025) · European Journal of Cancer · doi:10.1016/j.ejca.2025.115809 · Cited by 6
Heinrich, K., Stintzing, S., von Weikersthal, L. F., Decker, T. W., Kiani, A., Kaiser, F., Al‐Batran, S., Heintges, T., Lerchenmueller, C., Kahl, C., et al. (2025) · European Journal of Cancer · doi:10.1016/j.ejca.2025.116133 · Cited by 6
Metadata
- Authors
- Venook, A. P., Niedzwiecki, D., Lenz, H.-J., Innocenti, F., Fruth, B., Meyerhardt, J. A., Schrag, D., Greene, C., O'Neil, B. H., Atkins, J. N., Berry, S., Polite, B. N., O'Reilly, E. M., Goldberg, R. M., Hochster, H. S., Schilsky, R. L., Bertagnolli, M. M., El-Khoueiry, A. B., Watson, P., Benson, A. B., Mulkerin, D. L., Mayer, R. J., & Blanke, C.
- Affiliations
- University of California, San Francisco (US)
- Duke University (US)
- University of Southern California (US)
- University of North Carolina at Chapel Hill (US)
- Mayo Clinic (US)
- Dana-Farber/Partners CancerCare, Boston, Massachusetts
- Indiana University, Simon Cancer Center, Indianapolis
- Southeastern Medical Oncology Center (US)
- Sunnybrook Health Science Centre (CA)
- University of Chicago Comprehensive Cancer Center, Chicago, Illinois
- Memorial Sloan Kettering Cancer Center (US)
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- Department of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut
- American Society of Clinical Oncology (US)
- Brigham and Women's Hospital (US)
- Kinston Medical Specialists (US)
- Northwestern University (US)
- University of Wisconsin–Madison (US)
- Oregon Health & Science University (US)
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2017-06-20
- Volume
- 317
- Issue
- 23
- Pages
- 2392
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC5545896
- OpenAlex
- W2712978371
- Cited by
- 898
- References
- 24
- Citations by year
- 2026: 66 · 2025: 76 · 2024: 87 · 2023: 104 · 2022: 118 · 2021: 118 · 2020: 122 · 2019: 107 · 2018: 82 · 2017: 16
- FWCI
- 39.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR001863)
- National Cancer Institute (U10CA180882, K05CA169384, U10CA180820, U10CA180791, U10CA180888, U10CA180836, U10CA180790, U10CA180830, U10CA180795, U10CA180850, R01CA149222, U10CA180838, U10CA180867, U10CA180821, U10CA180799)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Keywords
- metastatic colorectal cancer, KRAS wild-type, cetuximab, bevacizumab, first-line chemotherapy, mFOLFOX6, FOLFIRI, oxaliplatin, irinotecan, monoclonal antibodies, overall survival, progression-free survival, anti-EGFR therapy, anti-VEGF therapy, community oncology
- MeSH terms
- Bevacizumab, Cetuximab, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Canada, Leucovorin, Female, Fluorouracil, Humans, Male, Middle Aged, Organoplatinum Compounds, Genes, ras, United States, Colorectal Neoplasms, Treatment Outcome, Disease-Free Survival, Angiogenesis Inhibitors, Kaplan-Meier Estimate
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
