Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial

Tabernero, Josep; Lenz, Heinz Josef; Siena, Salvatore; Sobrero, Alberto; Falcone, Alfredo; Ychou, Marc; Humblet, Yves; Bouché, Olivier; Mineur, Laurent; Barone, Carlo; Adenis, Antoine; Yoshino, Takayuki; Goldberg, Richard M.; Sargent, Daniel J.; Wagner, Andrea; Laurent, Dirk; Teufel, Michael; Jeffers, Michael; Grothey, Axel; Cutsem, Éric Van

doi:10.1016/s1470-2045(15)00138-2

Cited by 301 publications

(260 citation statements)

References 46 publications

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“…Chemotherapy containing anti-EGFR antibody was administered in 29 patients. KRAS mutations at codon 12/13 in cancer tissues were detected in 41% of the patients and frequency of mutation types was similar to that reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database (20,21). With plasma DNA, among patients in whom KRAS mutations were positive in cancer tissue, KRAS mutations were detected in 33% using MBP-QP and 33% using PCR-rSSO ( Table 2).…”

Section: Kras Mutations Were Detected With Plasma Dna Isolated From Csupporting

confidence: 80%

“…These data indicate that the anti-cancer effect of chemotherapy containing anti-EGFR antibody is correlated with the mutant load. The detection rate using MBP-QP was relatively low compared to other detection systems previously reported [21,23,24]. It seems to be related to the fact that patients in our study included non-metastatic cancer patients, and sample collection was conducted during chemotherapy in 2/3 of those patients.…”

Section: Discussionmentioning

confidence: 74%

“…T790 M mutation was detected with plasma DNA in 53% of lung adenocarcinoma patients who acquired resistance to EGFR-TKI in our retrospective study, and in 40% of those in a prospective, multiinstitutional study [17,19]. The new detection system for KRAS mutations used in this paper contained five types of mutations in codon 12 as well as G13D, which together cover 98% of KRAS mutations in colorectal cancer [20,21]. The goal of our study was to investigate the potential for monitoring KRAS mutations during treatment with anti-EGFR antibodies.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 80%

“…Mutation status of KRAS with plasma DNA was analyzed after the start of chemotherapy using the MBP-QP and PCR-rSSO methods. White and black arrows in BKRAS mutation in plasma DNA^indicate the peaks for KRAS wild type and mutant type, respectively plasma DNA in from 76% to 98% of cases using these detection methods [21,23,24]. According to results using digital PCR, tumor derived DNA was detected in more than 75% of colorectal cancer patients, and the detection rate was equivalent to advanced pancreas, ovarian, breast, and gastroesophageal cancers [24].…”

Section: Discussionmentioning

confidence: 99%

“…According to results using digital PCR, tumor derived DNA was detected in more than 75% of colorectal cancer patients, and the detection rate was equivalent to advanced pancreas, ovarian, breast, and gastroesophageal cancers [24]. KRAS mutations with plasma DNA are sometimes detected even if KRAS mutations were not found in cancer tissues [21]. Technology for mutation detection has progressed recently, and the sensitivity has been reported to be less than 0.01% with some methods.…”

Section: Discussionmentioning

confidence: 99%

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Detection of KRAS Mutations in Plasma DNA Using a fully Automated Rapid Detection System in Colorectal Cancer Patients

Hosoya

Matsusaka

Kashiwada

et al. 2017

Pathol. Oncol. Res.

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KRAS mutations have been recognized as predictive markers of primary resistance to anti-EGFR-antibodies in colorectal cancer patients. In addition, newly detected KRAS mutations have been reported to be related with acquired resistance to chemotherapy containing anti-EGFR antibody. Considering this evidence, monitoring of KRAS mutations is indispensable for making treatment decisions, and the method should be non-invasive allowing repeated examinations. Recently, we established a novel automated sensitive detection system for KRAS mutations, named mutation-biased PCR quenching probe system (MBP-QP). The goal of our study was to investigate the potential for monitoring KRAS mutations during treatment with anti-EGFR antibodies. The detection limit of MBP-QP using a control plasmid containing KRAS mutations was 1-9 copies, and 0.05-0.3% mutant plasmid was detectable in a mixture of wild type and mutants. One-hundred twenty colorectal cancer patients were genotyped for KRAS mutations with MBP-QP as well as polymerase chain reaction reverse sequence-specific oligonucleotide (PCR-rSSO), which has already been applied to cancer tissue samples in the clinical setting. Concordance rates between plasma DNA and cancer tissues were 68% with MBP-QP and 66% with PCR-rSSO, indicating that these systems are equivalent in terms of detecting KRAS mutations with plasma DNA. KRAS mutations in plasma DNA were frequently observed in systemic metastatic cancer patients, and in three patients KRAS mutations appeared after chemotherapy containing anti-EGFR antibody. A prospective study is needed for clarifying whether KRAS mutations detected in plasma DNA are predictive markers of treatment efficacy with anti-EGFR antibody.

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Section: Kras Mutations Were Detected With Plasma Dna Isolated From Csupporting

confidence: 80%

Section: Discussionmentioning

confidence: 74%

Section: Electronic Supplementary Materialsmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Detection of KRAS Mutations in Plasma DNA Using a fully Automated Rapid Detection System in Colorectal Cancer Patients

Hosoya

Matsusaka

Kashiwada

et al. 2017

Pathol. Oncol. Res.

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Genomic Analysis of Plasma Cell-Free DNA in Patients With Cancer

2017

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Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

et al. 2017

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An accurate blood‐based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti‐EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood‐based RAS mutation testing is a viable alternative to standard‐of‐care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin‐fixed paraffin‐embedded) tumor samples. Discordant tissue RAS results were re‐examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood‐based RAS mutation testing is a viable alternative to tissue‐based RAS testing.

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Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial

Abstract: Bayer HealthCare Pharmaceuticals.

Cited by 301 publications

References 46 publications

Detection of KRAS Mutations in Plasma DNA Using a fully Automated Rapid Detection System in Colorectal Cancer Patients

Detection of KRAS Mutations in Plasma DNA Using a fully Automated Rapid Detection System in Colorectal Cancer Patients

Genomic Analysis of Plasma Cell-Free DNA in Patients With Cancer

Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

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