scholarly journals Influence of first line chemotherapy strategy depending on primary tumor location in metastatic colorectal cancer

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Zoé Tharin ◽  
Julie Blanc ◽  
Ikram Charifi Alaoui ◽  
Aurélie Bertaut ◽  
Francois Ghiringhelli
2021 ◽  
Author(s):  
George Kafatos ◽  
Victoria Banks ◽  
Peter Burdon ◽  
David Neasham ◽  
Kimberly A Lowe ◽  
...  

Background: Advances in therapies for patients with metastatic colorectal cancer (mCRC) and improved understanding of prognostic and predictive factors have impacted treatment decisions. Materials & methods: This study used a large oncology database to investigate patterns of monoclonal antibody (mAb) plus chemotherapy treatment in France, Germany, Italy, Spain and the UK in mCRC patients treated in first line in 2018. Results: Anti-EGFR mAbs were most often administered to patients with RAS wild-type mCRC and those with left-sided tumors, while anti-VEGF mAbs were preferred in RAS mutant and right-sided tumors. Adopted treatment strategies differed between countries, largely due to reimbursement. Conclusion: Biomarker status and primary tumor location steered treatment decisions in first line. Adopted treatment strategies differed between participating countries.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 683-683 ◽  
Author(s):  
Wen-zhuo He ◽  
Qiong Yang ◽  
Chang Jiang ◽  
Fang-xin Liao ◽  
Shou-sheng Liu ◽  
...  

683 Background: There is currently no consensus about whether bevacizumab effectiveness is associated with the primary tumor location of metastatic colorectal cancer (mCRC). The aim of this study was to assess whether the primary tumor location was a predictor for bevacizumab treatment. Methods: From 2004 to 2013, 740 patients with mCRC treated with oxaliplatin / 5-FU / leucovorin (mFOLFOX6) or irinotecan / 5-FU / leucovorin (FOLFIRI) (CT group) and 244 patients treated with bevacizumab plus mFOLFOX6 or FOLFIRI (CT + B group) as first-line setting were included from Sun yat-sen university cancer center. Right-side colon cancers included those occurring in the cecum, ascending colon or transverse colon. Left-side colon cancers included those from descending or sigmoid colon. The primary outcome was overall survival (OS). Kaplan-Meier curves with log-rank tests were used to detect difference. All statistical tests were two sided. Results: 222 right-side colon, 259 left-side colon and 259 rectal cancer patients were included in CT group while 78 right-side colon, 86 left-side colon and 80 rectal cancer patients were included in CT + B group. Patients in CT + B group had similar OS compare with CT group only when the primary tumor located at right-side colon (median OS was 19.6 months for CT + B group versus 19.5 months for CT group, P = 0.269). For left-side colon cancer, significantly longer OS were observed in CT + B than CT group (22.3 months versus 21.9 months, P = 0.014). For rectal cancer patients, those in CT + B group also had longer OS than CT group (25.9 months versus 21.1 months, P = 0.005). Conclusions: Our data suggested that patients with right-side colon cancer could not get survival benefit from the addition of bevacizumab to first-line chemotherapy. Further data from randomized trials are needed to test our hypothesis. [Table: see text]


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 557-557 ◽  
Author(s):  
Qianqian Yu ◽  
Hong Qiu ◽  
Mingsheng Zhang ◽  
Xianglin Yuan

557 Background: Clinical trials including CALGB/SWOG 80405 and FIRE-3 reveal differences in overall survival (OS) for metastatic colorectal cancer (mCRC) patients treated with targeted therapy based on primary tumor location. We assessed the impact of tumor location on prognosis in a prospective series of patients with mCRC received FOLFIRI in first-line therapy. Methods: Patients treated with FOLFIRI were consecutively recruited between November 2010 and December 2014. Follow-up information was updated in February 2016 when 77.3% of the patients were deceased. We defined the right-sided colon = cecum to transverse colon, left-sided colon = splenic flexure to sigmoid descending colon, rectum = rectosigmoid plus rectal cancer, respectively. We measured median survival using Kaplan-Meier plots and 2-year survival probability using life tables. Associations between tumor locations and treatment outcomes were estimated using a Cox proportional hazards model. Age and gender were included in adjusted Cox models to estimate the hazard ratio (HR) for death of rectal and left-sided tumors relative to right-sided tumors. Results: Right-sided cancer had a shorter median survival (13.5 vs. 20.4 months) and worse 2-year survival probability (28% vs. 39%) than left-sided and rectal cancers, however the difference was of no statistical significance no matter in unadjusted (HR = 1.002, 95% CI 0.635-1.581) or adjusted models (HR = 1.037, 95% CI 0.657-1.639). Conclusions: mCRC patients with right-sided colon got comparative survival benefit from FOLFIRI in first-line treatment to the left-sided colon and rectum. This result needs to be validated in studies with larger sample size. Clinical trial information: NCT01282658.


2021 ◽  
Author(s):  
Annabel Helga Sophie Alig ◽  
Volker Heinemann ◽  
Michael Geissler ◽  
Ludwig Fischer von Weikersthal ◽  
Thomas Decker ◽  
...  

Abstract BackgroundPrimary tumor location (left vs. right) has prognostic and predictive impact on the therapeutic management of metastatic colorectal cancer (mCRC) in particular in the context of anti-epithelial growth factor receptor (anti-EGFR) antibodies. This analysis evaluates the relevance of exact segment-by-segment tumor location in patients with metastatic colorectal cancer on outcome and efficacy of anti-EGFR-antibodies.MethodsThis is a retrospective, pooled analysis of five randomized clinical trials (FIRE-1, CIOX, FIRE-3, XELAVIRI and VOLFI) treating metastatic colorectal cancer patients in a first-line setting, published between 2011-2019. Each trial was a multicentre, phase 2 or phase 3 trial in which patients with untreated metastatic colorectal cancer received chemotherapy regimens with or without monoclonal antibodies (anti-VEGF, anti-EGFR). Eligible were patients with histologically confirmed metastatic colorectal cancer in good performance status who were at least 18 years old. Individual data of 1809 patients with available exact primary tumor location were included into this analysis. Prognostic and predictive effects of primary tumor location were evaluated in uni- and multivariate analyses using the Kaplan Meier method, log rank tests, Cox regressions and logistic regressionsResults Exact primary tumor location is an important determinant of overall survival (OS) in mCRC patients (P<0.001). Multivariate analysis of RAS/BRAF wild-type metastatic colorectal cancer indicate that efficacy of anti-EGFR agents in terms of OS increases continuously from primary tumors located in the caecum (HR 2.63), ascending colon (HR 1.24), right flexure/transverse colon (HR 0.99), left flexure/descending colon (HR 0.91) to the sigmoid (HR 0.71) and rectum (HR 0.58), demonstrating significant benefit in sigmoid and rectal metastatic colorectal cancer, as well as clear detriment in caecum mCRC. Patients with BRAF V600E mutant disease arising from left-sided segments of the colorectum benefitted from EGFR-antibody treatment survival: hazard ratio for death in left-sided tumors: 0.42 (95% CI 0.19-0.92).Conclusions Primary tumor location of metastatic colorectal cancer affects prognosis. Anti-EGFR efficacy increases continuously from proximal to distal segments of the colorectum in metastatic colorectal cancer patients with RAS/BRAF wild-type and BRAF mutant tumors. Therefore, patients with BRAF mutant tumors of the distal segments may benefit from first-line Anti-EGFR-based therapy.Trial registrationFIRE1 trial registration ID n/aCIOX trial registration ID NCT00254137FIRE3 trial registration ID NCT00433927XELAVIRI trial registration ID NCT01249638VOLFI trial registration ID NCT01328171


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3572-3572 ◽  
Author(s):  
Mogens Karsboel Boisen ◽  
Christian Dehlendorff ◽  
Dorte Linnemann ◽  
Jim S. Larsen ◽  
Kell Oesterlind ◽  
...  

3572 Background: We aimed to identify tissue microRNAs (miRs) that could predict outcome for patients with metastatic colorectal cancer (mCRC) treated with first line bevacizumab (BEV) and chemotherapy (CT) but not for patients treated with CT alone. Methods: Patients with mCRC treated with first line capecitabine and oxaliplatin (CT) with or without BEV at ten hospitals were identified and data was extracted retrospectively. Formalin-fixed paraffin-embedded tissue samples from primary tumors were collected and RNA was purified from 3 x 10 µm sections, without micro-dissection. miR expression was measured using Applied Biosystems TaqMan Custom LDA cards profiling 22 selected miRs in duplicate. The 22 miRs were selected from a previous discovery study profiling 754 miRs. miR expression was related to time to disease progression (TTP) and overall survival (OS) in multivariate analyses using Cox proportional hazards models with adjustment for age, prior adjuvant treatment, and no. of metastatic sites. We have previously found that patients with primary tumors originating in the sigmoid colon and rectum (S+R) experienced a better outcome than patients with other primary tumor locations (caecum to descending colon) when treated with BEV, so our analyses were stratified by primary tumor location. Results: miR expression was measured in samples from 399 patients: 155 samples from the original CT+BEV discovery study, 119 samples from a new CT+BEV cohort, and 125 samples from a CT alone cohort. Expression of miR-664 showed a significant positive association with increasing TTP, OS, and response rate (RR), but only in the cohort of patients with sigmoid colon- and rectal primary tumors treated with CT+BEV (n=183). Conclusions: We have identified a subgroup of patients with mCRC that are likely to benefit from BEV addition to first line CT using the combined information of location of the primary tumor and expression level of miR-664. [Table: see text]


2017 ◽  
Vol 28 ◽  
pp. iii118-iii119
Author(s):  
Gonçalo Atalaia ◽  
Marta Vaz Baptista ◽  
Tiago Tomás ◽  
Susana Almeida ◽  
Inês Eiriz ◽  
...  

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