Prognostic impact of primary tumor location on survival time in patients (pts) with metastatic colorectal cancer (mCRC) treated with cetuximab plus oxaliplatin-based chemotherapy: A subgroup analysis of the JACCRO CC-05/06 (original) (raw)
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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 ...
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% ...
Primary tumor location as a prognostic factor in metastatic colorectal cancer
Journal of the National Cancer Institute, 2015
We sought to clarify the prognostic impact of primary tumor location in metastatic colorectal cancer (mCRC). We evaluated the association between tumor location and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy ± bevacizumab in three independent cohorts: a prospective pharmacogenetic study (PROVETTA) and two randomized phase III trials, AVF2107g and NO16966. Cancers proximal or distal of the splenic flexure were classified as right-sided or left-sided, respectively. The primary end point was overall survival (OS). Data were analyzed with Cox proportional hazards and logistic regression models. All statistical tests were two-sided. Among evaluable patients in the PROVETTA (n = 200), AVF2107g (n = 559), and NO16966 (n = 1268) studies, 72.0%, 63.1%, and 73.7% had left-sided tumors, respectively. In PROVETTA, patients with left-sided tumors had superior OS (left-sided vs right-sided: hazard ratio [HR] = .44, 95% confidence interval [CI]...
Right- and left-sided colorectal cancers respond differently to cetuximab
Chinese journal of cancer, 2015
Right-sided colon cancer (RSCC) and left-sided colorectal cancer (LSCRC) differ with respect to their biology and genomic patterns. This study aimed to examine whether the primary tumor location is associated with the response to cetuximab in patients with metastatic colorectal cancer (mCRC). Patients with mCRC treated with cetuximab and standard chemotherapy as first- or second-line treatments were compared with randomly chosen patients who were treated with chemotherapy alone between 2005 and 2013. The main outcome measures were the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The differences in the outcome were analyzed by using the chi-squared test, Student's t test, and Kaplan-Meier method. The treatment results of 206 patients with mCRC treated with cetuximab and standard chemotherapy as first- or second-line treatments were compared with those of 210 patients who were treated with chemotherapy alone. As a first-line treatment, c...
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.
Critical reviews in oncology/hematology, 2018
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. It has been reported that left- and right-sided CRC harbor varying disease characteristics, which leads to a difference in prognosis and response to therapy. Recently, there have been retrospective studies about tumor location in metastatic CRC (mCRC) and its potential to predict the effect of anti-vascular endothelial growth factor and anti-epidermal growth factor receptor (anti-EGFR) therapies. In this review, we provide a comprehensive overview of the latest trials studying the predictive value of primary tumor location in mCRC and discuss biomarkers that might be associated with the differences in treatment response. Although data need to be interpreted with caution due to the absence of randomized trials stratified based on tumor location, patients with left-sided CRC seem to benefit more from anti-EGFR therapy than patients with right-sided CRC. Further clinical trials, stratified for tumor loca...
The Lancet Oncology
Background The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival. Methods New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m² administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m² administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m² repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m² administered intravenously over 2 h and oral capecitabine 1000 mg/m² twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m² intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m² every 2 weeks with regimen one and three or a loading dose of 400 mg/m² followed by a weekly infusion of 250 mg/m² with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-totreat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367.