PD-033 Right-sided colon cancer is associated with increased frequency of KRAS mutation and with a poor outcome in patients with metastatic disease treated in the first line with bevacizumab and chemotherapy

Ostřížková, Lenka; Petruželka, Luboš; Hejduk, Karel; Zdražilová-Dubská, Lenka; Vočka, Michal; Brančíková, Dagmar; Bencsiková, Beatrix; Vyzula, Rostislav; Obermannová, Radka

doi:10.1093/annonc/mdw200.33

Cited by 2 publications

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“…We contacted the authors of these studies for data availability and received relevant data from five studies . A total of 44 studies were therefore included in the narrative review and meta‐analyses. The characteristics of the included studies are presented in Table .…”

Section: Resultsmentioning

confidence: 99%

“…Also, KRAS mutant tumors had poorer OS than wild‐type tumors among left‐sided tumors, but improved OS and PFS compared to wild‐type among right‐sided tumors . However, several studies evaluated the prognostic impact of tumor sidedness regardless of mutation status . In exploratory meta‐analyses summarizing the results of these studies, right‐sided mCRC tumors had significantly decreased OS (HR: 1.64, 95% CI: 1.43‐1.88) and PFS (HR: 1.33, 95% CI: 1.15‐1.55) compared to left‐sided tumors.…”

Section: Resultsmentioning

confidence: 99%

“…31,67 However, several studies evaluated the prognostic impact of tumor sidedness regardless of mutation status. 6,7,49,58,[66][67][68]70 In exploratory meta-analyses summarizing the results of these studies, right-sided mCRC tumors had significantly decreased OS (HR: 1.64, 95% CI: 1.43-1.88) and PFS (HR: 1.33, 95% CI: 1.15-1.55) compared to leftsided tumors.…”

Section: Resultsmentioning

confidence: 99%

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Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis

et al. 2019

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Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti-epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta-analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty-four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta-analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left-sided tumors, 41.3% among right-sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left-sided tumors, 46.3% among right-sided tumors; P < .0001) and BRAF mutations (4.3% among left-sided tumors, 16.3% among right-sided tumors; P < .0001). Among right-sided tumors, the prevalence of RAS and KRAS mutations varied significantly by study design, with higher prevalence among observational studies than clinical trials, and there was significant variation by study location for the prevalence of KRAS mutations in left-sided tumors and the prevalence of BRAF mutations in right-sided tumors. These results help to better characterize the mCRC population to better inform clinicians and researchers. Few of the included studies reported overall or progression-free survival (PFS) by both tumor sidedness and mutation status. As both of these factors may have prognostic impact, future studies should consider evaluating survival by these variables. K E Y W O R D S BRAF, KRAS, metastatic colorectal cancer, RAS, tumor sidedness | 1045 BYLSMA et AL. ORCID Lauren C. Bylsmahttps://orcid.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis

et al. 2019

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“…Roselli et al emphasized the unexplained lack of association between clinical outcome and CD8 + T cells [36] that we also observed when baseline circulating immune parameters from mCRC patients were analyzed irrespective of primary tumor sidedness. Nevertheless, and based on our previous findings of poor clinical outcome of mCRC patients with primary tumors in the right colon [37] and the differential impact of KRAS status for 1st-line anti-VEGF-based therapy in primary right vs. left-sided mCRC [38], we analyzed circulating immune cells in the context of primary tumor sidedness, revealing that the association of previously identified Treg-associated biomarkers, as well as a baseline number of circulating CD8 + T cells, with clinical outcome of 1st-line anti-VEGF-based therapy is particularly strong in mCRC patients with primary tumor in the right colon.…”

Section: Discussionmentioning

confidence: 99%

Circulating T cell subsets are associated with clinical outcome of anti-VEGF-based 1st-line treatment of metastatic colorectal cancer patients: a prospective study with focus on primary tumor sidedness

et al. 2019

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Background In a prospective study with long-term follow-up, we analyzed circulating T cell subsets in patients with metastatic colorectal cancer (mCRC) in the context of primary tumor sidedness, KRAS status, and clinical outcome. Our primary goal was to investigate whether baseline levels of circulating T cell subsets serve as a potential biomarker of clinical outcome of mCRC patients treated with an anti-VEGF-based regimen. Methods The study group consisted of 36 patients with colorectal adenocarcinoma who started first-line chemotherapy with bevacizumab for metastatic disease. We quantified T cell subsets including Tregs and CD8 + T cells in the peripheral blood prior to therapy initiation. Clinical outcome was evaluated as progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Results 1) mCRC patients with KRAS wt tumors had higher proportions of circulating CD8 + cytotoxic T cells among all T cells but also higher measures of T regulatory (Treg) cells such as absolute count and a higher proportion of Tregs in the CD4 + subset. 2) A low proportion of circulating Tregs among CD4 + cells, and a high CD8:Treg ratio at initiation of VEGF-targeting therapy, were associated with favorable clinical outcome. 3) In a subset of patients with primarily right-sided mCRC, superior PFS and OS were observed when the CD8:Treg ratio was high. Conclusions The baseline level of circulating immune cells predicts clinical outcome of 1st-line treatment with the anti-VEGF angio/immunomodulatory agent bevacizumab. Circulating immune biomarkers, namely the CD8:Treg ratio, identified patients in the right-sided mCRC subgroup with favorable outcome following treatment with 1st-line anti-VEGF treatment. Electronic supplementary material The online version of this article (10.1186/s12885-019-5909-5) contains supplementary material, which is available to authorized users.

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PD-033 Right-sided colon cancer is associated with increased frequency of KRAS mutation and with a poor outcome in patients with metastatic disease treated in the first line with bevacizumab and chemotherapy

Abstract: poster discussions PD À 033 Right-sided colon cancer is associated with increased frequency of KRAS mutation and with a poor outcome in patients with metastatic disease treated in the first line with bevacizumab and chemotherapy

Cited by 2 publications

References 0 publications

Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis

Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta‐analysis

Circulating T cell subsets are associated with clinical outcome of anti-VEGF-based 1st-line treatment of metastatic colorectal cancer patients: a prospective study with focus on primary tumor sidedness

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