Dataset Information

Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy.

ABSTRACT: There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter "Italian Trial in Advanced Colorectal Cancer (ITACa)", randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B). RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX2), ephrin type-B receptor 4 (EPHB4), hypoxia-inducible factor 1-alpha (HIF-1?), lactate dehydrogenase (LDH), and high-sensitivity C reactive protein (hs-CRP); and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017). Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors.

SUBMITTER: Ulivi P

PROVIDER: S-EPMC5486063 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy.

Ulivi Paola P Scarpi Emanuela E Chiadini Elisa E Marisi Giorgia G Valgiusti Martina M Capelli Laura L Casadei Gardini Andrea A Monti Manlio M Ruscelli Silvia S Frassineti Giovanni Luca GL Calistri Daniele D Amadori Dino D Passardi Alessandro A

International journal of molecular sciences 20170609 6

There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter "Italian Trial in Advanced Colorectal Cancer (ITACa)", randomized to receive first-line chemotherapy ( ...[more]

PMID: 28598398

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Project description:BackgroundDoublets plus anti-epidermal growth factor receptors (EGFRs) are the preferred upfront option for patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC). Initial therapy with FOLFOXIRI-bevacizumab is superior to doublets plus bevacizumab independently from primary tumor sidedness and RAS/BRAF status. No randomized comparison between FOLFOXIRI-bevacizumab versus doublets plus anti-EGFRs is available in left-sided RAS/BRAF wild-type mCRC.Materials and methodsWe selected patients with left-sided RAS and BRAF wild-type mCRC treated with first-line FOLFOX-panitumumab or FOLFOXIRI-bevacizumab in five randomized trials: Valentino, TRIBE, TRIBE2, STEAM, and CHARTA. A propensity score-based analysis was performed to compare FOLFOXIRI-bevacizumab with FOLFOX-panitumumab.ResultsA total of 185 patients received FOLFOX-panitumumab and 132 received FOLFOXIRI-bevacizumab. Median progression-free survival (PFS) and median overall survival (OS) were 13.3 and 33.1 months in the FOLFOXIRI-bevacizumab group compared with 11.4 and 30.3 months in the FOLFOX-panitumumab group (propensity score-adjusted hazard ratio (HR) for PFS, 0.82; 95% confidence interval (CI), 0.64-1.04; p = .11; propensity score-adjusted HR for OS, 0.80; 95% CI, 0.59-1.08; p = .14). No significant differences in overall response rate and disease control rate were observed. A statistically nonsignificant difference in favor of FOLFOXIRI-bevacizumab was observed for OS after secondary resection of metastases. Chemotherapy-related adverse events were more frequent in the FOLFOXIRI-bevacizumab group, with specific regard to grade 3 and 4 neutropenia (48% vs. 26%, adjusted p = .001).ConclusionAlthough randomized comparison is lacking, both FOLFOXIRI-bevacizumab and FOLFOX-panitumumab are valuable treatment options in left-sided RAS/BRAF wild-type mCRC.Implications for practiceA propensity score-based analysis of five trials was performed to compare FOLFOX-panitumumab versus FOLFOXIRI-bevacizumab in left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC). No significant differences were observed, but FOLFOXIRI-bevacizumab achieved numerically superior survival outcomes versus FOLFOX-panitumumab. Chemotherapy-related adverse events were more frequent in the FOLFOXIRI-bevacizumab group. These observations suggest that although doublet chemotherapy plus anti-EGFRs remains the preferred treatment in patients with left-sided RAS/BRAF wild-type mCRC, FOLFOXIRI-bevacizumab is a valuable option able to provide similar, if not better, outcomes at the price of a moderate increase in toxicity and may be adopted based on patients' preference and potential impact on quality of life.

Dataset Information

Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy.

Publications

Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy.

Similar Datasets

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