Correlation of measurements of tumor heterogeneity based on next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) with clinical outcomes in STEAM, a prospective, randomized, multicenter study in metastatic colorectal cancer (mCRC).

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 3545-3545 ◽  
Author(s):  
Stephanie Yaung ◽  
Nalin Tikoo ◽  
Alan Nicholas ◽  
Nicolas Sommer ◽  
Johanna C. Bendell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Multicenter Study ◽  
Tumor Heterogeneity ◽  
Circulating Tumor Dna ◽  
Next Generation Sequencing Ngs ◽  
Tumor Dna ◽  
Generation Sequencing

Next Generation Sequencing of Circulating Tumor DNA Can Optimize Second Line Treatment in RAS Wild Type Metastatic Colorectal Cancer after Progression on Anti-EGFR Therapy: Time to Rethink Our Approach

2022 ◽  
Author(s):  
Davide Mauri ◽  
Konstantinos Kamposioras ◽  
Dimitris Matthaios ◽  
Maria Tolia ◽  
Ioanna Nixon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Metastatic Colorectal Cancer ◽  
Circulating Tumor Dna ◽  
Clinical Approach ◽  
Line Treatment ◽  
Next Generation ◽  
Wild Type ◽  
Tumor Dna ◽  
Generation Sequencing

Background Management of Raswild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge. Development of treatment resistance with prevalence of pre-existing RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. Summary The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation Next Generation Sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify drugable mutations or recovery of RAS-wildness. In this opinion paper we summarize with critical thinking the clinical approach to be followed after the failure of first line treatment in Ras wild-type CRC tumors with the use of NGS. Key Messages Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of Ras wildness, and targeted approach of specific mutations (BRAF inhibitors) amplifications (anti-Her2 treatment) or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic colorectal cancer and guide clinical decisions. NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.

RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment With Anti-EGFR Antibodies in Patients With Metastatic Colorectal Cancer

2020 ◽  
pp. 898-911
Author(s):  
Yu Sunakawa ◽  
Masato Nakamura ◽  
Masahiro Ishizaki ◽  
Masato Kataoka ◽  
Hironaga Satake ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Circulating Tumor Dna ◽  
Wild Type ◽  
Phase Ii Trials ◽  
Ras Mutation ◽  
Ras Mutations ◽  
Ras Status ◽  
Tumor Dna

PURPOSE Several trials have evaluated the efficacy of rechallenge treatment with anti–epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with metastatic colorectal cancer (mCRC). A recent trial indicated that RAS status in circulating tumor DNA (ctDNA) may potentially predict patients with RAS wild-type mCRC resistant to anti-EGFR mAb who would benefit from rechallenge treatment, and the findings should be further investigated. MATERIAL AND METHODS We enrolled patients whose plasma samples were collected in prospective phase II trials, the JACCRO CC-08 (n = 36) and CC-09 (n = 25), which evaluated rechallenge chemotherapy with anti-EGFR mAb for KRAS wild-type mCRC. RAS in ctDNA was analyzed at the time points of baseline, 8 weeks, and progression using OncoBEAM RAS CRC kit. RESULTS Sixteen patients were enrolled in this study, with a response rate of 0% and a disease control rate (DCR) of 62.5%. RAS mutations were found at baseline in six patients. The DCR was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation at baseline. Patients with RAS mutation at baseline had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without RAS mutation (median PFS, 2.3 v 4.7 months; hazard ratio [HR], 6.2; P = .013; median OS, 3.8 v 16.0 months; HR, 12.4; P = .0028). Six of 10 patients without RAS mutation at baseline acquired RAS mutations at progression. Postprogression survival after rechallenge treatment was numerically shorter in patients with RAS mutation at progression. CONCLUSION RAS status in ctDNA was significantly associated with clinical outcomes in patients with mCRC receiving rechallenge treatment with anti-EGFR mAb. These findings could support the clinical utility of OncoBEAM RAS CRC kits for anti-EGFR mAb rechallenge in RAS wild-type mCRC.

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