Mutational profiles of metastatic colorectal cancer treated with <scp>FOLFIRI</scp> plus cetuximab or bevacizumab before and after secondary resection (<scp>AIO KRK</scp> 0306; <scp>FIRE</scp>‐3)

Stahler, Arndt; Heinemann, Volker; Holch, Julian Walter; Einem, Jobst C. von; Westphalen, C. Benedikt; Heinrich, Kathrin; Schlieker, Laura; Jelas, Ivan; Alig, Annabel Helga Sophie; Fischer, Laura E.; Weiss, Lena; Modest, Dominik Paul; Weikersthal, Ludwig Fischer von; Decker, Thomas; Kiani, Alexander; Moehler, Markus; Kaiser, Florian; Kirchner, Thomas; Jung, Andreas; Stintzing, Sebastian

doi:10.1002/ijc.33747

Cited by 3 publications

(3 citation statements)

References 37 publications

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“…On subgroup analysis, patients with a synchronous disease showed better DFS compared to metachronous disease. 42 The role of biologics (Anti-EGFR, Anti-VEGF) patients with resectable metastases is not proven with even detrimental effects in some trials, 43 thus it is not recommended as a part of peri-operative or adjuvant treatment. 44 The definition of "potentially resectable" metastatic disease is based mainly on consensus recommendations.…”

Section: Recommendations and Discussionmentioning

confidence: 99%

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020

Rashad¹,

Abdulla²,

Farouk³

et al. 2022

CMAR

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Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second cause of cancer related mortality. Treatment options for patients with metastatic CRC (mCRC) expanded during the last two decades, with introduction of new chemotherapeutic and targeted agents. Egypt is a lower middle-income country; Egyptian health care system is fragmented with wide diversity in drug availability and reimbursement policies across different health care providing facilities. We report the results of consensus recommendations for treatment of patients with metastatic colorectal cancer developed by Egyptian Foundation of Medical Sciences (EFMS), aiming to harmonize clinical practice through structured expert consensus-based recommendations consistent with the national status. EFMS recommendations could be utilized in other countries with similar economic status. Methods: EFMS recommendations were developed using a modified Delphi process, with three rounds of voting till the final recommendations were approved. A non-systematic review of literature was conducted before generating the provisional statements. Content experts were asked to vote on some recommendations in two different resource groups (restricted resources and non-restricted resources). External review board of experts from a low income and lower-middle countries voted on the applicability of EFMS recommendations in their countries. Results:The current recommendations highlighted the discrepancy in health care between restricted and non-restricted resources with expected survival loss and quality of life deterioration. Access to targeted agents in first line is very limited in governmental institutions, and no access to agents approved for third line in patients who failed oxaliplatin and irinotecan containing regimens for patients treated in restricted resource settings. Conclusion: Management of mCRC in developing countries is a challenge. The currently available resource-stratified guidelines developed by international cancer societies represent a valuable decision-making tool, adaptation to national status in each country based on healthcare system status is required.

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Section: Recommendations and Discussionmentioning

confidence: 99%

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020

Rashad¹,

Abdulla²,

Farouk³

et al. 2022

CMAR

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“…Using formalin-fixed paraffin-embedded (FFPE) samples of primary tumour tissue, gene expression analysis was carried out using ALMAC’s Xcel TM gene- expression array at ALMACs laboratories [ 23 ]. All analyses were approved by the ethics committee of the Ludwig-Maximilians-University, Munich (#186-15).…”

Section: Methodsmentioning

confidence: 99%

EMT-Related Genes Have No Prognostic Relevance in Metastatic Colorectal Cancer as Opposed to Stage II/III: Analysis of the Randomised, Phase III Trial FIRE-3 (AIO KRK 0306; FIRE-3)

Pretzsch

Stintzing

Bender

et al. 2022

Cancers

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Introduction: There is no standard treatment after resection of colorectal liver metastases and the role of systemic therapy remains controversial. To avoid over- or undertreatment, proper risk stratification with regard to postoperative treatment strategy is highly needed. We recently demonstrated the prognostic relevance of EMT-related (epithelial-mesenchymal transition) genes in stage II/III CRC. As EMT is a major step in CRC progression, we now aimed to analyse the prognostic relevance of EMT-related genes in stage IV CRC using the study cohort of the FIRE-3 trial, an open-label multi-centre randomised controlled phase III trial of patients with metastatic CRC. Methods: Overall and progression free survival were considered as endpoints (n = 350). To investigate the prognostic relevance of EMT-related genes on either endpoint, we compared predictive performance of different models using clinical data only to models using gene data in addition to clinical data, expecting better predictive performance if EMT-related genes have prognostic value. In addition to baseline models (Kaplan Meier (KM), (regularised) Cox), Random Survival Forest (RSF), and gradient boosted trees (GBT) were fit to the data. Repeated, nested five-fold cross-validation was used for hyperparameter optimisation and performance evaluation. Predictive performance was measured by the integrated Brier score (IBS). Results: The baseline KM model showed the best performance (OS: 0.250, PFS: 0.251). None of the other models were able to outperform the KM when using clinical data only according to the IBS scores (OS: 0.253 (Cox), 0.256 (RSF), 0.284 (GBT); PFS: 0.254 (Cox), 0.256 (RSF), 0.276 (GBT)). When adding gene data, performance of GBT improved slightly (OS: 0.262 vs. 0.284; PFS: 0.268 vs. 0.276), however, none of the models performed better than the KM baseline. Conclusion: Overall, the results suggest that the prognostic relevance of EMT-related genes may be stage-dependent and that EMT-related genes have no prognostic relevance in stage IV CRC.

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“…The emergence of activating KRAS mutations is a well-known (but not unique) mechanism of resistance to anti-EGFR therapy. For example, a retrospective analysis of the FIRE-3 clinical study (bevacizumab plus FOLFIRI or cetuximab plus FOLFIRI as first-line treatment for mCRC) has reported that a group of cetuximab-treated patients acquired activating mutations[ 14 ]. Furthermore, whole-exome sequencing studies have revealed that treatment with chemotherapy and cetuximab can be associated with a mutational signature (known as SBS17b) driving mutations in KRAS / NRAS and EGFR genes, resulting in resistance against this targeted therapy[ 15 ].…”

Section: Introductionmentioning

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

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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.

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Mutational profiles of metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab before and after secondary resection (AIO KRK 0306; FIRE‐3)

Cited by 3 publications

References 37 publications

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020

EMT-Related Genes Have No Prognostic Relevance in Metastatic Colorectal Cancer as Opposed to Stage II/III: Analysis of the Randomised, Phase III Trial FIRE-3 (AIO KRK 0306; FIRE-3)

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

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