Randomized Phase II Study of Cetuximab and Bevacizumab in Combination with Two Regimens of Paclitaxel and Carboplatin in Chemonaive Patients with Stage IIIB/IV Non–Small-Cell Lung Cancer

Bonomi, Philip; Mace, Joseph R.; Mandanas, Romeo A.; Min, Myo; Olsen, Mark R.; Youssoufian, Hagop; Katz, Terry; Sheth, Grishma; Lee, Hyun Jung

doi:10.1097/jto.0b013e318282ded5

Cited by 14 publications

(6 citation statements)

References 18 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bevacizumab, a humanized mAb directed against vascular endothelial growth factor (VEGF), was the first angiogenesis inhibitor approved for first-line treatment of patients with non-squamous NSCLC based on data from two studies that demonstrated ∼ 2 months of improvements in PFS and an improvement in OS, with results later replicated in Chinese patients with non-squamous NSCLC [ 53–55 ]. In a randomized phase II trial, cetuximab plus bevacizumab for the treatment of chemotherapy-naïve patients with advanced non-squamous NSCLC showed a prolonged median PFS of 6.05 months when combined with six cycles of chemotherapy [ 56 ]. It is important to note, however, that bevacizumab is contraindicated for treatment of patients with SqCLC due to a heightened risk of life-threatening pulmonary hemorrhage in this patient population [ 3 , 57 ].…”

Section: Egfr-directed Mabs In Combination With Antiangiogenic Agentsmentioning

confidence: 99%

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer

et al. 2018

View full text Add to dashboard Cite

BackgroundUpregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs.DesignRandomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or antiangiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized.ResultsData from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥200) and/or gene copy numbers of EGFR (e.g. ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with antiangiogenic agents.ConclusionsTherapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or antiangiogenic agents remain limited.

show abstract

Section: Egfr-directed Mabs In Combination With Antiangiogenic Agentsmentioning

confidence: 99%

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Studies have also examined cetuximab treatment for non-small cell lung cancer (NSCLC), breast cancer, and hepatocellular carcinoma (HCC). 5–7…”

Section: Introductionmentioning

confidence: 99%

Incidence of cetuximab-related infusion reactions in oncology patients treated at the University of North Carolina Cancer Hospital

Keating

Walko

Stephenson

et al. 2013

J Oncol Pharm Pract

View full text Add to dashboard Cite

Rates of hypersensitivity reaction at UNC are similar to rates seen in other areas of the southeastern United States and higher than in other regions of the United States and Europe. Rates of both hypersensitivity reactions and grade 3 to 4 hypersensitivity reactions have not substantially changed over time. Geography, allergy history, and perhaps smoking or cancer type may help predict who will react to cetuximab. Steroids should be strongly considered as premedication in addition to diphenhydramine.

show abstract

“…Bevacizumab binds to VEGF and prevents the proliferation of endothelial cells and formation of blood vessels, as well as decreases the blood supply and reduces tumor interstitial pressure. Thus, the ability of chemotherapy to reach the tumor is increased by the combinatorial treatment 20,70–73…”

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

View full text Add to dashboard Cite

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.

show abstract

Randomized Phase II Study of Cetuximab and Bevacizumab in Combination with Two Regimens of Paclitaxel and Carboplatin in Chemonaive Patients with Stage IIIB/IV Non–Small-Cell Lung Cancer

Abstract: Both the regimens showed expected PFS and numerically comparable overall survival. Quality of life was similar in the two arms, and both the regimens were well tolerated.

Cited by 14 publications

References 18 publications

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer

Incidence of cetuximab-related infusion reactions in oncology patients treated at the University of North Carolina Cancer Hospital

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

Contact Info

Product

Resources

About