Emergence of RAS mutations in patients with metastatic colorectal cancer receiving cetuximab-based treatment: a study protocol

Chen, Shang Hung; Tsai, Hsiang Lin; Jiang, Jeng Kai; Sung, Yung Chuan; Huang, Ching Wen; Yeh, Yu Min; Chen, Li Tzong; Wang, Jaw‐Yuan

doi:10.1186/s12885-019-5826-7

Cited by 5 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another important advantage of liquid biopsy is the possibility to monitor and identify mutations that will arise from the primary tumor to the metastatic lesion ( Siravegna et al, 2015 ). Several reports have demonstrated the possibility to monitor, through liquid biopsy, the arising of resistance mutations during treatment with anti-EGFR therapies ( Gargalionis and Papavassiliou, 2017 ; Khan et al, 2018 ; Chen et al, 2019 ; Kastrisiou et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: The Added Value of Liquid Biopsy in Advanced Colorectal Cancer From Clinical Case Experiences

et al. 2021

View full text Add to dashboard Cite

Liquid biopsy represents a valid strategy for tumor molecular characterization. It gives the opportunity to bypass tumor heterogeneity, to monitor tumor characteristics during the course of treatment, and to perform the analysis even when tumor tissue is not available or inadequate. In the clinical practice of metastatic colorectal cancer, tumor molecular characterization is crucial for patient management, as RAS and BRAF status could influence the treatment choice. Although for this type of cancer tumor tissue is usually available at diagnosis, liquid biopsy could give complementary information and could permit monitoring of the mutation status during the course of treatment. At present, there are no clinical indications for its use in clinical practice. However, we report four clinical cases for which liquid biopsy analysis gave integrative information with respect to tumor tissue characterization, which permits us to understand the unresponsiveness of patients to treatment, with potential implications in patient’s management.

show abstract

Section: Discussionmentioning

confidence: 99%

Case Report: The Added Value of Liquid Biopsy in Advanced Colorectal Cancer From Clinical Case Experiences

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Pretreatment tissue sections were re-evaluated for the RAS genotype using this technique if inconsistency regarding RAS was detected between the tissue and blood samples of the same patient. The study design, patient characteristics, inclusion and exclusion criteria, and detailed treatment regimens, including patient withdrawal data, were described in our study protocol [ 32 ]. This protocol is briefly outlined in Supplementary Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Tumour responses were typically assessed after every six cycles of the interventional regimen. Response measurements are detailed in our protocol [ 32 ], and were based on the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

The emergence of RAS mutations in patients with RAS wild-type mCRC receiving cetuximab as first-line treatment: a noninterventional, uncontrolled multicenter study

Tsai¹,

Lin²,

Sung³

et al. 2023

Br J Cancer

Self Cite

View full text Add to dashboard Cite

Absrtact Background Patients treated with anti-epidermal growth factor receptor (anti-EGFR) will ultimately develop acquired resistance promoted by clonal selection, mainly the emergence of mutations in the MAPK pathway (mostly RAS mutations). Baseline assessment of RAS mutations in the blood of patients correlates well with RAS tumour tissue testing and is currently an alternative option in routine clinical practice to guide first-line therapy. The aim of this study was the prevalence of acquired genomic alterations detected in the auxiliary tool of ctDNA testing and investigated the role of RAS ctDNA status for detecting tumour response and predicting benefit to anti-EGFR therapy. Methods Only patients with concordant wild-type formalin-fixed, paraffin-embedded (FFPE) tumour tissue and baseline ctDNA RAS wild-type were included. RAS mutations in plasma were evaluated using MassARRAY platform. Blood samples were collected at baseline, every 3 months during first-line treatment, and at disease progression. The primary endpoint was the detection rate of RAS mutations during cetuximab treatment. The correlation between response and survival outcomes and the emergence of circulating RAS mutations was also analysed. Results The detection rate of RAS mutations during treatment was 9.3% (10/108). RAS mutations detection occurred a median of 3 months prior to radiologic documentation. The subgroup of patients with RAS mutations exhibited significantly inferior progression-free survival and overall survival (P = 0.002 and 0.027, respectively) but the baseline characteristics, response rates, disease control rates, and metastatectomy were not significant (all P > 0.05). Conclusions We demonstrated that RAS ctDNA status might be a valuable biomarker for detecting early tumour response and predicting benefit to anti-EGFR therapy. Clinical Trial Registration: NCT03401957 (January 17, 2018).

show abstract

“…Clinical studies are currently being conducted to standardize the frequency of sampling and interpretation of results. Two prospective studies have attempted to establish the prognostic value of liquid biopsy protocols; both studies including periodic three-monthly ctDNA analyses and clinical follow-up in CRC wt KRAS patients exposed to 5-fluorouracil regimens plus anti-EGFR antibodies[ 72 , 73 ]. Finally, current international guidelines, such as ESMO, have concluded that although there is insufficient evidence to recommend follow-up with liquid biopsy, such analysis could be useful for detecting secondary resistance to anti-EFGR[ 4 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

Liquid biopsy to detect resistance mutations against anti-epidermal growth factor receptor therapy in metastatic colorectal cancer

Valenzuela¹,

Burotto²,

Marcelain³

et al. 2022

WJGO

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a major cause of mortality worldwide, associated with a steadily growing prevalence. Notably, the identification of KRAS , NRAS , and BRAF mutations has markedly improved targeted CRC therapy by affording treatments directed against the epidermal growth factor receptor (EGFR) and other anti-angiogenic therapies. However, the survival benefit conferred by these therapies remains variable and difficult to predict, owing to the high level of molecular heterogeneity among patients with CRC. Although classification into consensus molecular subtypes could optimize response prediction to targeted therapies, the acquisition of resistance mutations to targeted therapy is, in part, responsible for the lack of response in some patients. However, the acquisition of such mutations can induce challenges in clinical practice. The utility of liquid biopsy to detect resistance mutations against anti-EGFR therapy has recently been described. This approach may constitute a new standard in the decision algorithm for targeted CRC therapy.

show abstract

Emergence of RAS mutations in patients with metastatic colorectal cancer receiving cetuximab-based treatment: a study protocol

Cited by 5 publications

References 33 publications

Case Report: The Added Value of Liquid Biopsy in Advanced Colorectal Cancer From Clinical Case Experiences

Case Report: The Added Value of Liquid Biopsy in Advanced Colorectal Cancer From Clinical Case Experiences

The emergence of RAS mutations in patients with RAS wild-type mCRC receiving cetuximab as first-line treatment: a noninterventional, uncontrolled multicenter study

Liquid biopsy to detect resistance mutations against anti-epidermal growth factor receptor therapy in metastatic colorectal cancer

Contact Info

Product

Resources

About