Ramucirumab in the second-line treatment of metastatic colorectal cancer: A narrative review of literature from clinical trials

Chen, Chou-Pin; Ke, Tao-Wei; Cheng, Rebecca; Wang, Jaw-Yuan

doi:10.21037/tcr-20-608

Cited by 11Colorectal Cancer Treatments and StudiesAngiogenesis and VEGF in CancerColorectal Cancer Surgical Treatments

Ramucirumab in the second-line treatment of metastatic colorectal cancer: A narrative review of literature from clinical trials

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Chen, Chou-Pin, Ke, Tao-Wei, Cheng, Rebecca, Wang, Jaw-Yuan·2020·Translational Cancer Research

DOI 10.21037/tcr-20-608PMC PMC8798650

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Abstract

Abstract: The development of new anti-angiogenic agents targeting the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor pathways has greatly expanded the therapeutic options for patients with metastatic colorectal cancer (mCRC). Although these new agents have considerably improved survival outcomes compared with conventional chemotherapeutic regimens, the optimal integration of these drugs into the management of patients with mCRC continues to develop. One particular challenge is the identification of patient subgroups that will benefit from treatment with a specific targeted agent. In RAISE, a phase III randomized, placebo-controlled clinical trial, the VEGF receptor 2 antagonist ramucirumab in combination with fluorouracil plus leucovorin and irinotecan demonstrated efficacy as a second-line treatment for patients with mCRC. Ramucirumab is approved for the treatment of patients with mCRC in Taiwan but, due to lack of reimbursement, is often reserved for use as a third-line or later treatment. This narrative review of prespecified and post-hoc analyses of the RAISE study data, and data from other ramucirumab trials and real-world studies, summarizes the efficacy and tolerability of ramucirumab in the second-line treatment of different subpopulations of patients with mCRC. The aim was to identify patients most likely to benefit from treatment with second-line ramucirumab, with a view to illustrating the potential benefit of integrating this regimen into Taiwanese or Asian treatment practice.

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In RAISE, ramucirumab demonstrated directional improvements in mOS and mPFS in patients with mutant KRAS tumors, with significant improvement in mPFS in RAS mutant patients (p=0.021).
“Ramucirumab demonstrated directional improvements in mOS and mPFS compared to placebo in patients with mutant KRAS tumors. Notably, improvements in overall survival were observed with ramucirumab across all patients, including those with RAS/BRAF mutations, with a significant improvement in mPFS observed in the RAS mutant patients (p = 0.021) [36].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [36]

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Global patterns and trends in colorectal cancer incidence and mortality
Arnold, M., Sierra, M. S., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2016) · Gut · doi:10.1136/gutjnl-2015-310912 · Cited by 5,250 · see citing works
Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Van Cutsem, E., Cervantes, A., Nordlinger, B., & Arnold, D. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu260 · Cited by 1,167 · see citing works
Ramucirumab versus Placebo in Combination with Second-Line FOLFIRI in Patients with Metastatic Colorectal Carcinoma That Progressed during or after First-Line Therapy with Bevacizumab, Oxaliplatin, and a Fluoropyrimidine (RAISE): A Randomised, Double-Blind, Multicentre, Phase 3 Study
Tabernero, J., Yoshino, T., Cohn, A. L., Obermannova, R., Bodoky, G., Garcia-Carbonero, R., Ciuleanu, T.-E., Portnoy, D. C., Van Cutsem, E., Grothey, A., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70127-0 · Cited by 952 · see citing works
Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO–ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS
Yoshino, T., Arnold, D., Taniguchi, H., Pentheroudakis, G., Yamazaki, K., Xu, R.-H., Kim, T. W., Ismail, F., Tan, I. B., Yeh, K.-H., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdx738 · Cited by 573 · see citing works
Is right-sided colon cancer different to left-sided colorectal cancer? – A systematic review
Lee, G. H., Malietzis, G. A., Askari, A., Bernardo, D., Al-Hassi, H. O., & Clark, S. K. (2014) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2014.11.001 · Cited by 422 · see citing works
Exposure–Response Relationships of the Efficacy and Safety of Ipilimumab in Patients with Advanced Melanoma
Feng, Y., Roy, A., Masson, E., Chen, T., Humphrey, R. W., & Weber, J. S. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3243 · Cited by 183 · see citing works
Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study
Tabernero, J. M., Hozak, R. R., Yoshino, T., Cohn, A. L., Obermannova, R. L., Bodoky, G., García‐Carbonero, R., Ciuleanu, T., Portnoy, D. C., Prausová, J., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx767 · Cited by 106 · see citing works
CEA monitoring in colorectal cancer. What you should know.
Fakih, M., & Padmanabhan, A. (2006) · PubMed · Cited by 105 · see citing works
Activating KRAS Mutations and Overexpression of Epidermal Growth Factor Receptor as Independent Predictors in Metastatic Colorectal Cancer Patients Treated With Cetuximab
Yen, L.-C., Uen, Y., Wu, D., Lu, C.-Y., Yu, F., Wu, I., Lin, S., & Wang, J. (2010) · Annals of Surgery · doi:10.1097/sla.0b013e3181bc9d96 · Cited by 89 · see citing works
Self-citation
The relationship between primary tumor sidedness and prognosis in colorectal cancer.
Schrag, D., Weng, S., Brooks, G. A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.3505 · Cited by 77 · see citing works
Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression
Obermannova, R. L., Cutsem, E. V., Yoshino, T., Bodoky, G., Prausová, J., García‐Carbonero, R., Ciuleanu, T., Alfonso, P., Portnoy, D. C., Cohn, A. L., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw402 · Cited by 71 · see citing works
Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE—a global phase III study
Yoshino, T., Portnoy, D. C., Obermannova, R. L., Bodoky, G., Prausová, J., García‐Carbonero, R., Ciuleanu, T., Alfonso, P. G., Cohn, A. L., Cutsem, E. V., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy461 · Cited by 64 · see citing works
Exposure–Response Relationship of T-DM1: Insight Into Dose Optimization for Patients With HER2-Positive Metastatic Breast Cancer
Wang, J., Song, P., Schrieber, S. J., Liu, Q., Xu, Q., Blumenthal, G. M., Kordestani, L. A., Cortazar, P., Ibrahim, A., Justice, R. L., et al. (2014) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2014.24 · Cited by 63 · see citing works
Self-citation
Options for metastatic colorectal cancer beyond the second line of treatment
Foubert, F., Matysiak‐Budnik, T., & Touchefeu, Y. (2013) · Digestive and Liver Disease · doi:10.1016/j.dld.2013.07.002 · Cited by 50 · see citing works
Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab‐based treatment response in metastatic colorectal cancer
Prager, G. W., Brämswig, K. H., Martel, A., Unseld, M., Heinze, G., Brodowicz, T., Scheithauer, W., Kornek, G. V., & Zielinski, C. C. (2014) · Cancer Science · doi:10.1111/cas.12451 · Cited by 49 · see citing works
Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer
Tabernero, J. M., Ohtsu, A., Muro, K., et al. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0895 · Cited by 48 · see citing works
KRAS mutation testing in clinical practice
Perincheri, S., & Hui, P. (2014) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2015.986102 · Cited by 46 · see citing works
Beyond KRAS: Predictive factors of the efficacy of anti-EGFR monoclonal antibodies in the treatment of metastatic colorectal cancer
Stefano, A. D. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i29.9732 · Cited by 43 · see citing works
Exposure-response analysis of rilotumumab in gastric cancer: the role of tumour MET expression
Zhu, M., Tang, R. F., Doshi, S., et al. (2015) · British Journal of Cancer · doi:10.1038/bjc.2014.649 · Cited by 42 · see citing works
Randomized phase II study of modified FOLFOX-6 in combination with ramucirumab or icrucumab as second-line therapy in patients with metastatic colorectal cancer after disease progression on first-line irinotecan-based therapy
Moore, M., Gill, S., Asmis, T. R., Berry, S. R., Burkes, R. L., Zbuk, K. M., Alcindor, T., Jeyakumar, A. S., Chan, T., Rao, S., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw412 · Cited by 38 · see citing works
CEA response is associated with tumor response and survival in patients with KRAS exon 2 wild-type and extended RAS wild-type metastatic colorectal cancer receiving first-line FOLFIRI plus cetuximab or bevacizumab (FIRE-3 trial)
Michl, M., Stintzing, S., von Weikersthal, L. F., Decker, T. W., Kiani, A., Vehling-Kaiser, U., Al-Batran, S.-E., Heintges, T., Lerchenmueller, C., Kahl, C., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw222 · Cited by 36 · see citing works
Baseline Carcinoembryonic Antigen as a Predictive Factor of Ramucirumab Efficacy in RAISE, a Second-Line Metastatic Colorectal Carcinoma Phase III Trial
Yoshino, T., Obermannová, R., Bodoky, G., Garcia-Carbonero, R., Ciuleanu, T., Portnoy, D. C., Kim, T. W., Hsu, Y., Ferry, D., Nasroulah, F., et al. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2017.03.007 · Cited by 27 · see citing works
Exposure–response relationship for ramucirumab from the randomized, double-blind, phase 3 REVEL trial (docetaxel versus docetaxel plus ramucirumab) in second-line treatment of metastatic non-small cell lung cancer
Smit, E. F., Garon, E. B., Reck, M., Cappuzzo, F., Bidoli, P., Cohen, R. B., Gao, L., O’Brien, L. M., Lee, P., Zimmermann, A. H., et al. (2018) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-018-3560-5 · Cited by 23 · see citing works
Prognostic factors for metastatic colorectal cancer patients undergoing irinotecan-based second-line chemotherapy.
Shitara, K., Matsuo, K., Yokota, T., et al. (2011) · PubMed · Cited by 22 · see citing works
Association of baseline absolute neutrophil counts and survival in patients with metastatic colorectal cancer treated with second-line antiangiogenic therapies: exploratory analyses of the RAISE trial and validation in an electronic medical record data set
Grothey, A. F., Yoshino, T., Bodoky, G., Ciuleanu, T., García‐Carbonero, R., Alfonso, P. G., Cutsem, E. V., Muro, K., Mytelka, D. S., Li, L., et al. (2018) · ESMO Open · doi:10.1136/esmoopen-2018-000347 · Cited by 21 · see citing works
Efficacy and safety of ramucirumab plus modified FOLFIRI for metastatic colorectal cancer
Yoshihiro, T., Kusaba, H., Makiyama, A., Kobayashi, K., Uenomachi, M., Ito, M., Doi, Y., Mitsugi, K., Aikawa, T., Takayoshi, K., et al. (2019) · International Journal of Clinical Oncology · doi:10.1007/s10147-018-01391-w · Cited by 19 · see citing works
Exposure–response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial
Cohn, A. L., Yoshino, T., Heinemann, V., Obermannova, R. L., Bodoky, G., Prausová, J., García‐Carbonero, R., Ciuleanu, T., Alfonso, P. G., Portnoy, D. C., et al. (2017) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-017-3380-z · Cited by 18 · see citing works
Second-line FOLFIRI plus ramucirumab with or without prior bevacizumab for patients with metastatic colorectal cancer
Suzuki, T., Shinozaki, E., Osumi, H., Nakayama, I., Ota, Y., Ichimura, T., Ogura, M., Wakatsuki, T., Ooki, A., Takahari, D., et al. (2019) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-019-03855-w · Cited by 14 · see citing works
Grade 3/4 neutropenia is a limiting factor in second-line FOLFIRI following FOLFOX4 failure in elderly patients with metastatic colorectal cancer
Kuboki, Y., Mizunuma, N., Ozaka, M., Ogura, M., Suenaga, M., Shinozaki, E., Matsusaka, S., Chin, K., Matsuura, M., & Hatake, K. (2011) · Oncology Letters · doi:10.3892/ol.2011.260 · Cited by 11 · see citing works
Effect of Early Adverse Events on Survival Outcomes of Patients with Metastatic Colorectal Cancer Treated with Ramucirumab
Lim, H. H., Hopkins, A. M., Rowland, A., Yuen, H.-Y., Karapetis, C. S., & Sorich, M. J. (2019) · Targeted Oncology · doi:10.1007/s11523-019-00683-z · Cited by 9 · see citing works
An observational study of vascular endothelial growth factor inhibitors as second-line treatment for metastatic colorectal cancer treated with bevacizumab plus FOLFIRI beyond progression: the association with RAS mutation and tumor sidedness
Tsai, H., Huang, C., Ma, C., Su, W., Chang, T., Chen, P.-J., Yeh, Y., & Wang, J. (2019) · Translational Cancer Research · doi:10.21037/tcr.2019.09.59 · Cited by 6 · see citing works
Self-citation
[Experience of Ramucirumab plus FOLFIRI as Second-Line Treatment for Metastatic Colorectal Cancer in Our Hospital].
Hagino, S., Miyata, T., & Sakamoto, K. (2017) · PubMed · Cited by 2 · see citing works

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Heun, J. M., & Holen, K. D. (2007) · Clinical Colorectal Cancer · doi:10.3816/ccc.2007.n.019 · Cited by 45 · see citing works
The effectiveness of cetuximab and panitumumab when combined with FOLFIRI in second-line treatment of KRAS wild type metastatic colorectal cancers. Single centre experience
Gürsoy, P., Çakar, B., Almuradova, E., et al. (2020) · Journal of Chemotherapy · doi:10.1080/1120009x.2020.1861531 · Cited by 2 · see citing works
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Grothey, A. F. (2008) · Biologics · doi:10.2147/btt.s1980 · Cited by 49 · see citing works
ASPECCT: panitumumab versus cetuximab for colorectal cancer
Goss, P. E., Bl, L.-B., Wang, J., et al. (2014)
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Authors: Chen, C.-P., Ke, T.-W., Cheng, R., & Wang, J.-Y.
Affiliations: Taichung Veterans General Hospital (TW)
China Medical University Hospital (TW)
Kaohsiung Medical University (TW)
Corresponding author: Wang, Jaw-Yuan
ORCID: Ke, Tao-Wei
Wang, Jaw-Yuan
Venue: Translational Cancer Research
Publisher: AME Publishing Company
Published: 2020-09
Volume: 9
Issue: 9
Pages: 5645-5654
ISSN: 2218-676X (ISSN-L)
2219-6803
DOI: 10.21037/tcr-20-608
PMC: PMC8798650
OpenAlex: W3083694408
Cited by: 11
References: 32
Citations by year: 2025: 5 · 2024: 4 · 2022: 1 · 2021: 1
FWCI: 0.05
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: cc-by-nc-nd
Locations: Translational Cancer Research (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: Eli Lilly and Company
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
Keywords: ramucirumab, metastatic colorectal cancer, second-line therapy, anti-angiogenic therapy, RAISE trial, irinotecan, patient subgroups, treatment efficacy and tolerability, reimbursement

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Ramucirumab in the second-line treatment of metastatic colorectal cancer: A narrative review of literature from clinical trials

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