Awareness of KRAS testing by oncologists and panitumumab use in colorectal cancer patients: A European survey.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 547-547
Author(s):  
Jorg Trojan ◽  
Aliki Taylor ◽  
Jan-Henrik Terwey ◽  
Gerry Downey ◽  
George Kafatos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Wild Type ◽  
Nras Mutation ◽  
Mutation Status ◽  
Kras Status ◽  
Level Of Knowledge ◽  
High Level ◽  
Colorectal Cancer Patients ◽  
Kras Mutation Status

547 Background: Panitumumab (Pmab) is licensed for treatment in metastatic colorectal cancer (mCRC) patients with wild type KRAS mutation status (US) and wild type RAS (KRAS and NRAS) mutation status (most other countries). To resolve uncertainties about KRAS testing, a survey and medical records review (MRR) are being carried out in Europe in three rounds: the first two rounds (2012-2013) evaluated KRAS testing and round 3 is evaluating RAS testing. These studies are specific obligations in Europe for the conditional marketing authorization for Pmab. Here we present results of rounds 1 and 2. Methods: Eligible oncologists were contacted by telephone in nine European countries (France, Germany, Italy, Spain, Czech Republic, Netherlands, Belgium, Denmark, and Sweden). To be eligible, the physician was required to be a practicing oncologist and have prescribed Pmab to mCRC patients. Results: 299 of 301 (99.3%) oncologists participating in the survey were aware of the need to perform KRAS testing prior to first dose of Pmab and 294 (97.7%) were aware of patients’ KRAS mutation status prior to first dose. 283 of 301 (94.0%) did not prescribe Pmab to mCRC patients with mutant or unknown KRAS status. 164 physicians administered Pmab simultaneously with oxaliplatin-containing chemotherapy to patients and 10 (6.1%) to patients with mutant or unknown KRAS status. 306 patients from 79 participating oncologists were included in the MRR. 302 of 306 mCRC patients (98.7%) were tested for KRAS tumor status, known by the oncologist before first dose of Pmab. 299 of 302 patients (99.0%) had wild-type KRAS tumor status. 83 of 85 patients (97.6%) treated with Pmab and oxaliplatin-containing chemotherapy had wild-type KRAS tumor status. 55 of 56 linked pathology laboratories (98.2%) participated in a Quality Assurance scheme; all used a CE marked or otherwise validated KRAS detection method. Conclusions: Results from both studies show a high level of knowledge among oncologists of the need for KRAS testing in mCRC patients prior to treatment with Pmab and the contraindication with oxaliplatin-containing chemotherapy with mutant or unknown KRAS tumour status. The final round of this study evaluating RAS testing in Europe is currently underway.

scholarly journals Timing of Aspirin and Other Nonsteroidal Anti-Inflammatory Drug Use Among Patients With Colorectal Cancer in Relation to Tumor Markers and Survival

2017 ◽  
Vol 35 (24) ◽  
pp. 2806-2813 ◽  
Author(s):  
Xinwei Hua ◽  
Amanda I. Phipps ◽  
Andrea N. Burnett-Hartman ◽  
Scott V. Adams ◽  
Sheetal Hardikar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Cpg Island ◽  
The United States ◽  
Wild Type ◽  
Cpg Island Methylator Phenotype ◽  
Mutation Status ◽  
Anti Inflammatory ◽  
Kras Mutation Status

Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status ( Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95% CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95% CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.

Use of the intensity of membranous EGFR staining by immunohistochemistry to predict the efficacy of chemotherapy containing cetuximab in KRAS wild-type patients with metastatic colorectal cancer: A retrospective analysis.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 516-516
Author(s):  
Naoki Takahashi ◽  
Yasuhide Yamada ◽  
Hirokazu Taniguchi ◽  
Kohei Akiyoshi ◽  
Yoshitaka Honma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Objective Response ◽  
Endoscopic Biopsy ◽  
Rank Test ◽  
Wild Type ◽  
Mutation Status ◽  
Significant Difference ◽  
Kras Mutation Status

516 Background: KRAS mutation status is a strong predictive factor for anti-EGFR monoclonal antibody therapy efficacy in metastatic colorectal cancer (mCRC). In the BOND trial, objective response rates to cetuximab in irinotecan-refractory mCRC were not significantly different based on the intensity of EGFR staining by immunohistrochemistry (IHC). However, this result was not evaluated by KRAS mutation status, so we retrospectively evaluated the relationship between the efficacy of chemotherapy containing cetuximab and the intensity of membranous EGFR staining in KRAS wild type (KRAS-WT) patients. Methods: Between August 2008 and July 2011, specimens of 391 CRC patients were collected by endoscopic biopsy or surgical resection. EGFR staining by IHC and genetic screening for KRAS status were performed and intensity of EGFR staining was scored by the Guidelines for Interpreting EGFR pharmDx, DAKO. We analyzed 94 KRAS-WT patients who received combination chemotherapy with an irinotecan-regimen plus cetuximab or cetuximab monotherapy and met the following criteria: histologically proven mCRC adenocarcinoma , at least 1 previous regimen of standard fluoropyrimidine - containing chemotherapy , ECOG PS score 0-2, and adequate hepatic and renal function. Patients were classified into 2 groups by intensity of EGFR staining: (A) absence of staining and weakly to moderately positive (IHC 1+ and IHC 2+), (B) strongly positive (IHC 3+). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and compared in Groups A and B by the log-rank test. Results: There was no significant difference in patient characteristics between the 2 groups except for primary site. The median PFS of Groups A (n=76) and B (n=18) were 5.4 months and 9.1 months (p= 0.029), the median OS was 8.1 months and 13.2 months (p=0.054) and response rate was 20.1% and 33.3%, respectively. Conclusions: In KRAS-WT patients with fluoropyrimidine-containing chemotherapy-refractory mCRC, strong intensity of EGFR staining by IHC might be predictive for efficacy of chemotherapy containing cetuximab.

Retrospective cohort study on the safety and efficacy of bevacizumab for metastatic colorectal cancer patients: The HGCSG0801 study—Efficacy of KRAS mutational status.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 680-680 ◽  
Author(s):  
Susumu Sogabe ◽  
Satoshi Yuki ◽  
Hideyuki Hayashi ◽  
Hirohito Naruse ◽  
Michio Nakamura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Statistical Tests ◽  
Progression Free Survival ◽  
Wild Type ◽  
Mutation Status ◽  
Free Survival ◽  
Mutational Status ◽  
Kras Mutation Status

680 Background: Mutations of the KRAS gene were identified as a prognostic marker in metastatic colorectal cancer(mCRC). Previously reported data suggests that the longer overall survival (OS) observed with bevacizumab(BV) treatment in mCRC is independent of alterations in the KRAS mutation status. So we analyzed efficacy of bevacizumab combined chemotherapy in mCRC relative to KRAS mutation status. Methods: In the retrospective analysis(n=212) of patients treated with BV(HGCSG0801), additional statistical analyses were done with data from KRAS mutation analyses. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine Progression-free survival(PFS) and OS. Log-rank test was used to compare with mutant or wild-type KRAS in terms of PFS and OS. All statistical tests were performed using SPSS. Results: KRAS status was assessed in 88 patients (41.5%). Response rate was 58.9% with wild-type and 62.5% with mutant KRAS, that was not significant(p=0.823). The median Progression-free survival was 11.5 months with wild-type and 11.5 months with mutant KRAS, that was not significant(p=0.222). And median OS was 31.8 months with wild-type and 27.5 months with mutant KRAS, that was not significant(p=0.760) as well. Similar results were seen among patients with first-line therapy. Conclusions: Bevacizumab provides clinical benefit in patients with mCRC expressing either mutant or wild-type KRAS.

Genetic analysis of KRAS mutation status in metastatic colorectal cancer patients

Neoplasma ◽  
2009 ◽  
Vol 56 (3) ◽  
pp. 275-278 ◽  
Author(s):  
K. Zavodna ◽  
M. Konecny ◽  
T. Krivulcik ◽  
S. Spanik ◽  
R. Behulova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Analysis ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Mutation Status ◽  
Colorectal Cancer Patients ◽  
Kras Mutation Status

A qPCR gene expression module test to predict resistance to cetuximab in colorectal cancers independent of KRAS mutation status.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14164-e14164
Author(s):  
Dan Rhodes ◽  
Sean Eddy ◽  
Paul Williams ◽  
Mark Tomilo ◽  
Seth Sadis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cancer Patients ◽  
Microarray Data ◽  
Kras Mutation ◽  
Mutation Status ◽  
Module Test ◽  
Colorectal Cancer Patients ◽  
Expression Module ◽  
Kras Mutation Status

e14164 Background: While KRAS mutation predicts resistance to anti-EGFR therapy in colorectal cancer, not all KRAS wild-type patients benefit from such therapy, suggesting that complementary biomarkers capable of identifying additional non-responsive patients would have clinical utility. Methods: To search for such a biomarker, we studied the relationship of cetuximab response with twelve gene expression modules, derived from an unsupervised analysis of 20 independent microarray datasets comprising more than 2,000 colorectal cancer patients. Each module represents a set of highly co-expressed genes related to an important aspect of colorectal cancer variability. Two cetuximab-treated cohorts were studied. The first was a Phase II clinical trial (Khambata-Ford et al, J Clin Oncol, 2007) with accompanying microarray data from pre-treatment biopsies. The second was a single-institution study of cetuximab response from which formalin-fixed paraffin-embedded primary tumor specimens were available. Results: In the first study, module scores were computed by averaging co-expressed module genes in the microarray data. In the second study, module scores were generated from a qPCR gene expression module test, OncoScore Colon, which quantifies modules by averaging three representative module genes relative to housekeeping controls. Notably, in both studies, the mesenchymal module was significantly associated with cetuximab resistance, with module positive patients tending to progress on cetuximab within 10 weeks. Additionally, the status of this module was independent of KRAS mutation status—KRAS mutations occurred in both module-positive and -negative patients. Future clinical studies will continue to test the predictive capacity of the module in regards to cetuximab resistance and other mechanisms. Conclusions: In summary, this study demonstrates the value of a gene expression module-based qPCR panel for stratifying colorectal cancer patients for treatment response, and suggests that our approach may have immediate utility for cetuximab treatment response prediction.

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