Epidermal growth factor receptor (EGFR) inhibitors for metastatic colorectal cancer

Chan, David; Segelov, Eva; Wong, Rachel; Smith, Annabel; Herbertson, Rebecca; Li, Bob T.; Tebbutt, Niall C.; Price, Tim; Pavlakis, Nick

doi:10.1002/14651858.cd007047.pub2

Cited by 82 publications

(82 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Because EGFR signaling has been recognized as an important player in CRC initiation and progression, EGFR inhibitors, which are effective in CRC harboring wild‐type RAS , have been used as one of the important molecular targeted therapies for CRC . Hence, RAS mutation analysis using plasma sample is expected to be applicable for the prediction of response to EGFR inhibitors and monitoring the change in RAS status of mCRC.…”

Section: Discussionmentioning

confidence: 99%

“…Because EGFR signaling has been recognized as an important player in CRC initiation and progression, [38][39][40] EGFR inhibitors, which are effective in CRC harboring wild-type RAS, have been used as one of the important molecular targeted therapies for CRC. [41][42][43] Hence, RAS mutation analysis using plasma sample is expected to be applicable for the prediction of response to EGFR inhibitors and monitoring the change in RAS status of mCRC. Although the timing of liquid biopsy (blood collection) after tissue biopsy in each patient was inconsistent in this study, the concordance rate of RAS status between tissue and matched plasma was 77.2% (78/101).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical relevance of circulating tumor DNA assessed through deep sequencing in patients with metastatic colorectal cancer

et al. 2018

View full text Add to dashboard Cite

Because circulating tumor DNA (ctDNA) studies focusing on only one or a few genes to monitor the disease progress or treatment response are unlikely to find its clinical significance, the development of cell‐free DNA (cfDNA) panel covering hundreds of mutation hot spots is important for the establishment of clinically practical ctDNA detection system. We enrolled 101 patients with metastatic colorectal cancer (mCRC) who received chemotherapy. Amplicon‐based genomic profiling of 14 genes, which are commonly mutated in CRC, in plasma by next‐generation sequencing (NGS) was carried out to evaluate the feasibility of this assay and was compared with their clinical parameters and RAS status in matched tissue samples. Somatic mutations of the 14 genes in plasma cfDNA were detected in 88 patients (87.1%) with mCRC. Mutations in TP53, KRAS, and APC genes were detected in 70 (69.3%), 39 (38.6%), and 24 (23.7%) patients, respectively. Mutant allele frequencies in plasma were significantly associated with metastasis (liver, P = 0.00004, lymph node, P = 0.008, number of metastatic organs, P = 0.0006), tumor markers (CEA, P = 0.000007, CA19‐9, P = 0.006, LDH, P = 0.00001), and tumor diameter (maximum, P = 0.00002, sum of diameter, P = 0.00009). The overall concordance rate of RAS status between ctDNA and matched tissue was 77.2% (78/101). Our data confirmed that mutant allele in cfDNA can be sensitively detected by amplicon‐based NGS system. These results suggest that ctDNA could be a novel diagnostic biomarker to monitor changes in mutational status and tumor burden in patients with mCRC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical relevance of circulating tumor DNA assessed through deep sequencing in patients with metastatic colorectal cancer

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Approximately 25% of patients undergo metastases at initial diagnosis, and almost 50% of patients with CRC will ultimately develop metastases 3. With the arrival of the era of molecular targeted therapy, the median survival time of patients with metastatic colorectal cancer (mCRC) has been extended to 30 months 4–6. However, most patients with mCRC have to receive palliative care due to the fact that no more medicine is available after they are ultimately refractory or intolerant to standard chemotherapies (fluoropyrimidine, irinotecan and oxaliplatin).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of TAS-102 in refractory metastatic colorectal cancer: a meta-analysis

Chen¹,

Wu²,

Lin³

et al. 2018

CMAR

View full text Add to dashboard Cite

BackgroundTAS-102 has been applied to metastatic colorectal cancer (mCRC) patients who had received at least two prior regimens of standard chemotherapy. This meta-analysis is designed to assess the efficacy and safety of TAS-102 in patients with mCRC.MethodsWe searched randomized controlled trials (RCTs) through PubMed, Embase, Web of Science and Cochrane clinical trial databases and clinicaltrial.gov from database initiation to March 2018. The overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and incidence of adverse events were summarized with the use of hazard ratio (HR) or risk ratio (RR).ResultsThree RCTs with 1318 patients were included. Results showed that TAS-102 significantly improved OS (HR 0.70, 95% confidence interval [CI] 0.62–0.79) and PFS (HR 0.46, 95% CI 0.40–0.52) in patients who were intolerant or refractory to fluoropyrimidine, irinotecan and oxaliplatin. The pooled odds ratio of DCR was 4.15 (95% CI 3.18–5.43). Notably, there were significant OS benefits both in patients with KRAS mutation (HR 0.76, 95% CI 0.63–0.92) and those with wild-type KRAS (HR 0.66, 95% CI 0.55–0.79). These benefits were also observed in patients with different numbers of metastatic sites. However, patients with >18 months since the diagnosis of first metastases seemed to have better OS (HR 0.65, 95% CI 0.55–0.77). The most common toxicities associated with TAS-102 were neutropenia (RR 116.51, 95% CI 23.51–577.33), leucopenia (RR 67.70, 95% CI 13.63–336.29), anemia (RR 4.28, 95% CI 2.70–6.79) and diarrhea (RR 5.10, 95% CI 1.40–18.61).ConclusionTAS-102 significantly improves OS, PFS and DCR in refractory mCRC patients with tolerable toxicity. Meanwhile, the OS benefits have nothing to do with KRAS status and the number of metastatic sites.

show abstract

“…Studies also show cetuximab and panitumumab Abs as effective for standard treatment in people with tumors of wild‐type KRAS CRC. For instance, patients with wild‐type KRAS EGFR‐positive tumors undergoing mAb therapies show a reduced risk of disease progression by 30%, risk of death by 12%, and the chance of tumor shrinkage is increased from 31% to 46% (Chan et al, 2017). Conversely, the same treatments in patients with KRAS‐ activating gene mutations in CRC result in unresponsiveness (Chan et al, 2017).…”

Section: Anti‐egfr Therapeutic Antibodies (Abs)mentioning

confidence: 99%

Epidermal growth factor receptor (EGFR) involvement in epithelial‐derived cancers and its current antibody‐based immunotherapies

London

Gallo

2020

Cell Biology International

View full text Add to dashboard Cite

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that is part of the family of tyrosine kinase receptors. The binding of EGFR to its cognate ligands leads to its autophosphorylation and subsequent activation of the signal transduction pathways involved in regulating cellular proliferation, differentiation, and survival. Accordingly, this receptor carries out both redundant and restricted functions in the germline development of mammals and in the maintenance of various adult tissues. Correspondingly, the loss of EGFR regulation results in many human diseases, with the most notable cancer. This receptor is overexpressed and/or mutated in multiple epithelial-derived tumors, and associated with poor prognosis and survival in cancer patients. Here, we discuss in detail the role of EGFR in specific epithelial-derived cancer pathologies; these include lung cancer, colorectal cancer, and squamous cell carcinomas. The development of multiple anticancer agents against EGFR diminished the progression and metastasis of tumors. Some of the most versatile therapeutic anti-EGFR agents include the monoclonal antibodies (mAbs), demonstrating success in clinical settings when used in combination with cytotoxic treatments, such as chemotherapy and/or radiation. We thus discuss the development and application of two of the most notable therapeutic mAbs, cetuximab, and panitumumab, currently utilized in various EGFR-related epithelial cancers.

show abstract

Epidermal growth factor receptor (EGFR) inhibitors for metastatic colorectal cancer

Cited by 82 publications

References 159 publications

Clinical relevance of circulating tumor DNA assessed through deep sequencing in patients with metastatic colorectal cancer

Clinical relevance of circulating tumor DNA assessed through deep sequencing in patients with metastatic colorectal cancer

Efficacy and safety of TAS-102 in refractory metastatic colorectal cancer: a meta-analysis

Epidermal growth factor receptor (EGFR) involvement in epithelial‐derived cancers and its current antibody‐based immunotherapies

Contact Info

Product

Resources

About