Reference | 1. Expert Opin Biol Ther. 2018 Apr;18(4):483-493. doi:
10.1080/14712598.2018.1452906.
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Cetuximab for treating non-small cell lung cancer.
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Mazzarella L(1), Guida A(1), Curigliano G(1).
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Author information:<br>
(1)a University of Milano, Department of Oncology and Hemato-Oncology, Division
of Early Drug Development for Innovative Therapies , European Institute of
Oncology , Milano , Italia.
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Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role
in epithelial cancer biology, and dictated the development of several targeting
agents. The mouse-human chimeric antibody Cetuximab was among the first to be
developed. After about two decades of clinical research it has gained a
significant place in the management of advanced colorectal and head and neck
cancers, whereas its development in non small cell lung cancer (NSCLC) has not
led to a place in routine clinical practice, because of marginal clinical
benefit despite statistically significant Phase III trials. Recent data from
ongoing trials suggest that more careful selection based on molecular markers
may identify good responders. Areas covered: In this article, the authors review
the literature concerning basic science studies identifying EGFR as a
therapeutic target, pharmacological development of Cetuximab, its
pharmacodynamics and pharmacokinetics, and clinical trials on Cetuximab in
NSCLC, focusing on recent findings on putative predictive biomarkers. Expert
opinion: Cetuximab currently has no role in NSCLC treatment outside of research
settings. We argue that failure to identify a predictive biomarker early on has
hampered its chances to enter routine practice. Although recent research
suggests benefit in highly selected patient subsets, its potential impact is
severely dampened by lack of regulatory body approval and the emergence of
competitors for the same niches.
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2. Adv Ther. 2018 Oct;35(10):1497-1509. doi: 10.1007/s12325-018-0791-0. Epub 2018
Sep 14.
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An Update of Efficacy and Safety of Cetuximab in Metastatic Colorectal Cancer: A
Narrative Review.
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Fornasier G(1), Francescon S(2), Baldo P(2).
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Author information:<br>
(1)Department of Pharmacy, Centro di Riferimento Oncologico (CRO) di
Aviano-IRCCS, National Cancer Institute, Aviano, Italy. [email protected].<br>
(2)Department of Pharmacy, Centro di Riferimento Oncologico (CRO) di
Aviano-IRCCS, National Cancer Institute, Aviano, Italy.
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Colorectal cancer is the second most common cancer, representing 13% of all
diagnosed cancers. Cetuximab is a recombinant chimeric monoclonal IgG1 antibody
and epidermal growth factor receptor (EGFR) inhibitor. Cetuximab is approved for
the first-line treatment in combination with chemotherapy or as a single agent
in patients who have failed or are intolerant to chemotherapy in patients with
EGFR-expressing, RAS wild-type metastatic colorectal cancer. Cetuximab efficacy
emerged from studies that were conducted to approve the drug. Cetuximab is well
tolerated; its toxicities are caused by its mechanism of action and the most
common adverse reaction is skin toxicity. The main purpose of this manuscript is
to present an update on the evidence-based summary of efficacy and safety and on
the cost-effectiveness of cetuximab. Furthermore, it suggests a management of
adverse drug reactions to improve the tolerability of the drug.
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3. Drugs Today (Barc). 2019 Nov;55(11):683-693. doi:
10.1358/dot.2019.55.11.3035584.
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Binimetinib, encorafenib and cetuximab (BEACON Trial) combination therapy for
patients with BRAF V600E-mutant metastatic colorectal cancer.
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Shahjehan F(1), Kamatham S(2), Chandrasekharan C(3), Kasi PM(4).
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Author information:<br>
(1)Department of Internal Medicine, Conemaugh Memorial Medical Center,
Johnstown, Pennsylvania, USA.<br>
(2)Department of Cancer Biology/Pathology, Wayne State University, Detroit,
Michigan, USA.<br>
(3)Department of Hematology/Oncology, University of Iowa, Iowa City, Iowa, USA.
(4)Department of Hematology/Oncology, University of Iowa, Iowa City, Iowa, USA.
[email protected].
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BRAF V600E mutations are associated with 8-10% of metastatic colorectal cancers
(mCRC) and carry a poor prognosis with limited therapeutic options. In contrast
to metastatic melanoma, BRAF inhibition alone or in combination with
mitogen-activated protein kinase kinase (MEK) inhibitors has shown little
utility in the treatment of BRAF V600E-mutant mCRC. This is secondary to
upstream activation of the epidermal growth factor receptor (EGFR) pathway and
other escape mechanisms. Combining RAF and MEK inhibitors with inhibition of the
EGFR pathway through an anti-EGFR receptor antibody (cetuximab) led to the
BEACON clinical trial (binimetinib, encorafenib and cetuximab). Trial patients
had undergone at least one prior line of chemotherapy. The trial met all its
endpoints and is now included in NCCN (National Comprehensive Cancer Network)
guidelines. Herein we provide updates in treatment options for patients with
BRAF V600E-mutant mCRC, focusing on the practice-changing BEACON-triplet
regimen, the first chemotherapy-free combination regimen for mCRC. This
combination is being explored frontline in the ANCHOR clinical trial.
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