An Open-Label Phase II Study Evaluating the Safety and Efficacy of Ramucirumab Combined With mFOLFOX-6 as First-Line Therapy for Metastatic Colorectal Cancer

Garcia-Carbonero, Rocío; Rivera, Fernando; Maurel, Joan; Ayoub, Jean-Pierre M.; Moore, Malcolm J.; Cervantes, Andrés; Asmis, Timothy R.; Schwartz, Jonathan D.; Nasroulah, Federico; Ballal, Shaila; Tabernero, Josep

doi:10.1634/theoncologist.2014-0028

Cited by 51 publications

(33 citation statements)

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“…Bevacizumab is targeted to the VEGF 20,21. Ramucirumab inhibits VEGF and VEGF receptor 22,23. Moreover, for the CD20 target, rituximab, ofatumumab, tositumomab, and ibritumomab tiuxetan24–26 are used.…”

Section: Supporting Treatment With Monoclonal Antibodiesmentioning

confidence: 99%

“…The binding of the monoclonal antibody inhibits the activation and signaling of these molecules/receptors 78. It is also believed that VEGF and VEGFR-2 mediated angiogenesis in colorectal cancer 22. Ramucirumab, in combination with FOLFIRI (irinotecan, folinic acid, and 5-FU), is indicated for the treatment of patients with mCRC with the disease in progression or after therapy with bevacizumab, oxaliplatin, and fluoropyrimidine.…”

Section: Supporting Treatment With Monoclonal Antibodiesmentioning

confidence: 99%

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Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies

Françoso¹,

Simioni²

2017

DDDT

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Colorectal cancer is considered a disease of the elderly population. Since the number of geriatric patients continues to rise, monoclonal antibody therapy is the most promising therapy in the recent research. Presently, the monoclonal antibodies most frequently used in the treatment of colorectal tumors are bevacizumab, cetuximab, panitumumab, and ramucirumab. Bevacizumab is a monoclonal antibody that acts on VEGF. Cetuximab and panitumumab act on EGFR. Ramucirumab binds directly to the ligand-binding pocket of VEGFR-2 to block the binding of VEGF-A, VEGF-C, and VEGF-D. These monoclonal antibodies, alone or in association with radiotherapy or chemotherapy, are presenting good results and are increasing patient survival, despite the side effects. Due to the limited number of molecules available, several studies are trying to develop new monoclonal antibodies for the treatment of colorectal tumors. Among those being studied, some recent molecules are in phase I and/or II trials and are yielding advantageous results, such as anti-DR5, anti-Fn14, anti-IGF-1R, anti-EGFR, anti-NRP1, and anti-A33 antibodies. This has been successful in reducing side effects and in treating nonresponsive patients.

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Section: Supporting Treatment With Monoclonal Antibodiesmentioning

confidence: 99%

Section: Supporting Treatment With Monoclonal Antibodiesmentioning

confidence: 99%

Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies

Françoso¹,

Simioni²

2017

DDDT

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“…The combination was shown to be efficacious with a median PFS of 11.5 mo and a median OS of 20.4 mo (Table 3). Neutropenia, hypertension, and neuropathy were the most commonly reported serious (grade 3-4) AEs [66] . The benefit of the addition of Ramucirumab to FOLFIRI in the second-line setting was recently evaluated in a large, randomized double-blind phase Ⅲ study (RAISE).…”

Section: Ziv-aflibercept (Vegf Trap)mentioning

confidence: 99%

Anti-angiogenic agents in metastatic colorectal cancer

Konda

Shum

Rajdev

2015

WJGO

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Colorectal cancer (CRC) is a major public health concern being the third leading cause of cancer mortality in the United States. The availability of better therapeutic options has led to a decline in cancer mortality in these patients. Surgical resection should be considered in all stages of the disease. The use of conversion therapy has made surgery a potentially curative option even in patients with initially unresectable metastatic disease. In this review we discuss the role of various antiangiogenic agents in patients with metastatic CRC (mCRC). We describe the mechanism of action of these agents, and the rationale for their use in combination with chemotherapy. We also review important clinical studies that have evaluated the safety and efficacy of these agents in mCRC patients. Despite the discovery of several promising anti-angiogenic agents, mCRC remains an incurable disease with a median overall survival of just over 2 years in patients exposed to all available treatment regimens. Further insights into tumor biology and tumor microenvironment may help improve outcomes in these patients. Core tip: Colorectal cancer is a major health concern and a leading cause of cancer mortality worldwide. New innovations have provided improved survival in recent years. In this review, we outline the novel anti-angiogenic agents and their respective roles in metastatic colorectal cancer. In addition to three agents approved by the Food and Drug Administration, several alternative anti-angiogenic agents hold promise for use in the metastatic setting.Konda B, Shum H, Rajdev L. Anti-angiogenic agents in metastatic colorectal cancer. World J Gastrointest Oncol 2015; 7(7): 71-86 Available from:

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“…In this study 48% of patients treated with ramucirumab discontinued treatment due to an adverse event or because of patient/physician decision (compared to 16% in the placebo arm) and this may have impacted the efficacy analysis for this trial. As ramucirumab did not increase rates of FOLFOX related toxicities in a colorectal cancer trial, an interaction with the patient population may be responsible for these findings (37). …”

Section: Toxicity Considerationsmentioning

confidence: 99%

Ramucirumab: Successfully Targeting Angiogenesis in Gastric Cancer

Javle

Smyth

Chau

2014

Clinical Cancer Research

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Gastric cancer is the fourth most common cancer globally and represents the second most common cause of cancer mortality. Early detection, aggressive surgical resection and postoperative adjuvant therapy has led to survival improvement for early stage gastric cancer, particularly in Asian countries. Unfortunately, advanced gastric cancer continues to pose a formidable challenge with few gains being reported recently. Trastuzumab was the first targeted agent to be approved for the treatment of advanced gastric cancer in 2010. The failure of the AVAGAST trial was a setback for anti-angiogenic therapy for this disease. Ramucirumab is a monoclonal antibody that binds to VEGF-R2 and prevents its activation. The recent REGARD trial was a randomized phase III trial of ramucirumab vs. placebo for patients with advanced, pre-treated gastric cancer that met its primary endpoint of increased overall survival. The toxicity of ramucirumab was modest in this setting, with an increased risk of grade 3 or higher hypertension (8% vs. 3%, with ramucirumab and placebo, respectively). The subsequent RAINBOW trial of paclitaxel plus ramucirumab vs. paclitaxel plus placebo for advanced pretreated gastric cancer confirmed the survival advantage of this antiangiogenic agent in gastric cancer. Ramucirumab is the first FDA approved therapy for advanced gastric cancer after prior chemotherapy.

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An Open-Label Phase II Study Evaluating the Safety and Efficacy of Ramucirumab Combined With mFOLFOX-6 as First-Line Therapy for Metastatic Colorectal Cancer

Cited by 51 publications

References 0 publications

Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies

Immunotherapy for the treatment of colorectal tumors: focus on approved and in-clinical-trial monoclonal antibodies

Anti-angiogenic agents in metastatic colorectal cancer

Ramucirumab: Successfully Targeting Angiogenesis in Gastric Cancer

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