Right- and left-sided colorectal cancers respond differently to cetuximab (original) (raw)
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Journal of Cancer Research and Clinical Oncology, 2014
Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial J. C. von Einem · V. Heinemann · L. Fischer von Weikersthal · U. Vehling-Kaiser · M. Stauch · 12/13 wild-type) and 46 patients right-sided primary tumors (of those 27 KRAS codon 12/13 wild-type). leftsided tumors were associated with significantly longer OS (p = 0.016, HR = 0.63) and PFS (p = 0.02, HR = 0.67) as compared to right-sided tumors. these effects were present in the KRAS codon 12/13 wild-type population (HR OS: 0.42; HR PFS: 0.54), while no impact of primary tumor location was evident in patients with KRAS codon 12/13 mutant tumors (HR OS: 1.3; HR PFS: 1.01). a significant interaction of KRAS status and primary tumor location concerning OS and PFS was observed. Conclusion Our findings suggest that primary tumor location and KRAS codon 12/13 mutational status interact on the outcome of patients with mCRC receiving cetuximabbased first-line therapy. left-sided primary tumor location might be a predictor of cetuximab efficacy.
Clinical colorectal cancer, 2016
Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed. A total of 110 patients were assessable for tumor location; 90 had lef...
Scientific Reports, 2020
The primary tumour location is an important prognostic factor for previously untreated metastatic colorectal cancer (mCRC). However, the predictive efficacies of primary tumour location, early tumour shrinkage (ETS), and depth of response (DpR) on mCRC treatment has not been fully evaluated. This study aimed to investigate the predictive efficacies of these traits in mCRC patients treated with first-line 5-fluorouracil-based chemotherapy plus biologic agents, namely, cetuximab and bevacizumab. This was a retrospective analysis of the medical records of 110 patients with pathology-documented unresectable mCRC. Patients with left-sided mCRC receiving any first-line regimen showed better overall survival (OS) than those with right-sided mCRC [33.3 vs 16.3 months; hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27–0.74; p < 0.001]. In patients with left-sided tumours, treatment with chemotherapy plus cetuximab yielded longer OS than chemotherapy plus bevacizumab (50.6 vs 27.8 ...
Number in 101 Advanced Colorectal Cancer Patients Treated with Chemotherapy Plus Cetuximab
2010
Background: Responsiveness to Cetuximab alone can be mediated by an increase of Epidermal Growth factor Receptor (EGFR) Gene Copy Number (GCN). Aim of this study was to assess the role of EGFR-GCN in advanced colorectal cancer (CRC) patients receiving chemotherapy plus Cetuximab. Methods: One hundred and one advanced CRC patients (43 untreated-and 58 pre-treated) were retrospectively studied by fluorescence in situ hybridization (FISH) to assess EGFR-GCN and by immunohistochemistry (IHC) to determine EGFR expression. Sixty-one out of 101 patients were evaluated also for k-ras status by direct sequencing. Clinical end-points were response rate (RR), progression-free survival (PFS) and overall survival (OS). Results: Increased EGFR-GCN was found in 60/101 (59%) tumor samples. There was no correlation between intensity of EGFR-IHC and EGFR-GCN (p = 0.43). Patients receiving chemotherapy plus Cetuximab as first line treatment had a RR of 70% (30/43) while it was 18% (10/56) in the group with previous lines of therapy (p < 0.0001). RR was observed in 29/ 60 (48%) of patients with increased EGFR-GCN and in 6/28 (21%) in those without (p = 0.02). At multivariate analyses, number of chemotherapy lines and increased EGFR-GCN were predictive of response; EGFR-IHC score, increased EGFR-GCN and number of chemotherapy lines were significantly associated with a significant better PFS. Response to therapy was the only prognostic predictive factor for OS. In the 60 patients analyzed for k-ras mutations, number of chemotherapy lines, increased EGFR-GCN and k-ras wild type status predicted a better PFS. Conclusion: In metastatic CRC patients treated with chemotherapy plus Cetuximab number of chemotherapy lines and increased EGFR-GCN were significantly associated with a better clinical outcome, independent of k-ras status.
Scientific Reports
The ITACa trial was designed to define the role of cetuximab (Cet) and bevacizumab (Bev) in combination with standard chemotherapy (CT, FOLFIRI or FOLFOX4) as first-and second-line treatment in metastatic colorectal cancer. All patients with WT KRAS tumors who had been enrolled in the first-line trial were randomized onto two independent second-line trials: CT or CT + Cet (study 2A) and CT + Bev or CT + Bev + Cet (study 2B). Patients with mutated KRAS were not eligible for randomization and were treated with CT alone (study 2A) or CT + Bev (study 2B). The primary endpoint was progression-free survival (PFS). 48 and 56 KRAS WT patients were randomized while 31 and 40 KRAS mutated patients were treated without randomization. Study 2A: median PFS was 3.4 (95%CI 2.3-4.6) and 6.2 (95%CI 4.3-7.8) months for the CT and CT + Cet arms, respectively, with a hazard ratio (HR) = 0.64 (95%CI 0.35-1.16, p = 0.144). Study 2B: median PFS was 7.7 (95%CI 4.1-10.1) and 4.9 (95%CI 3.2-7.0) months for CT + Bev and CT + Cet + Bev arms, respectively, with a HR = 1.31 (95%CI 0.76-2.26, p = 0.330). Notwithstanding limitations due to the small sample size, among patients with WT KRAS the addition of Cet to second-line CT increased PFS, whereas the addition of Cet to CT + Bev was associated with worse PFS. Colorectal cancer (CRC) is the third most commonly diagnosed cancer among males and the second among females worldwide 1. Combinations of fluorouracil (FU), leucovorin (LV) and oxaliplatin (FOLFOX), and of FU, LV, and irinotecan (FOLFIRI) are considered standard regimens for metastatic CRC (mCRC). Most patients with mCRC receive first-line chemotherapy (CT) and approximately 70% of those who progress after one line of CT will undergo at least one further line of systemic treatment 2-5 consisting in CT in combination with molecular-targeted agents directed against epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF). The use of antiVEGF agents (bevacizumab, Bev; Ziv-aflibercept and ramucirumab) in combination with second-line CT is supported by the positive results of several randomized phase III clinical trials 6-10. Similarly,
International journal of molecular sciences, 2017
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-1α), 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-infl...
2022
Purpose: In a sample of Middle Eastern population, we sought to evaluate whether survival outcomes for mCRC patients treated with systemic chemotherapy (SC) and, with and without biologic therapies (bevacizumab and cetuximab) are different between left and right-sided tumors. Methods: Ministry of National Guard- Health Affairs (MNG-HA) Cancer registry data was utilized to identify patients diagnosed with CRC between 2013 and 2016. Kaplan-Meier method and porosity score adjusted Cox proportional hazard models were used to assess survival for right and left-sided mCRC with and with BT. Results: A total of 196 mCRC patients with mean age of 64 years old, 57.65% male diagnosed from January 1, 2013, through December 31, 2016. The overall median survival for left-sided was significantly higher than right-sided mCRC tumors (P 0.03). mCRC patients treated with SC+BT were associated with decreased mortality only among patients with left-sided mCRC compared to right-sided mCRC (HR, 0.21; 95% ...