scholarly journals 415P Comparison of cetuximab every 2 weeks versus standard once-weekly administration for the first-line treatment of RAS wild-type metastatic colorectal cancer among patients with left- and right-sided primary tumor location

2021 ◽  
Vol 32 ◽  
pp. S542-S543
Author(s):  
S. Kasper ◽  
A-L. Cheng ◽  
M. Rouyer ◽  
C. Foch ◽  
F-X. Lamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Primary Tumor ◽  
Tumor Location ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
Weekly Administration ◽  
Primary Tumor Location ◽  
Left And Right ◽  
First Line Treatment

scholarly journals Impact of exact segment by segment primary tumor location status on anti-EGFR antibody first-line treatment efficacy in RAS/BRAF wild-type and BRAF mutant metastatic colorectal cancer. A pooled analysis of AIO studies FIRE-1, CIOX, FIRE-3, XELAVIRI, and VOLFI.

2021 ◽  
Author(s):  
Annabel Helga Sophie Alig ◽  
Volker Heinemann ◽  
Michael Geissler ◽  
Ludwig Fischer von Weikersthal ◽  
Thomas Decker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Tumor Location ◽  
Pooled Analysis ◽  
Trial Registration ◽  
Wild Type ◽  
First Line ◽  
Primary Tumor Location ◽  
Braf Mutant

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

PARADIGM study: A multicenter, randomized, phase III study of mFOLFOX6 plus panitumumab or bevacizumab as first-line treatment in patients with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 85-85
Author(s):  
Takayuki Yoshino ◽  
Hiroyuki Uetake ◽  
Katsuya Tsuchihara ◽  
Kohei Shitara ◽  
Kentaro Yamazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Primary Tumor ◽  
Phase Iii ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
Primary Analysis ◽  
Phase Iii Study ◽  
First Line Treatment

85 Background: The optimal choice of monoclonal antibodies (mAbs) for first-line treatment in patients (pts) with RAS ( KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC) remains controversial. The meta-analyses of subgroup analyses in phase III studies of pts with KRAS exon 2 wild-type mCRC suggested a longer overall survival (OS) with an anti-EGFR mAb over bevacizumab in pts with RAS wild-type mCRC or with left-sided primary tumors. However, there has been no prospective study comparing the two mAbs in these pt populations. This randomized phase III study was originally designed to demonstrate the superiority of panitumumab versus bevacizumab, both in combination with mFOLFOX6, for RAS wild-type mCRC, but we have revised the protocol to analyze efficacy in pts with a left-sided primary tumor as the primary (final) analysis. Methods: Eligible pts are aged 20-79 years with histologically/cytologically confirmed RAS wild-type chemotherapy-naive mCRC, and ECOG performance status 0-1. Between May 29, 2015 and Jun 8, 2017, 823 pts were randomized 1:1 to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6 by the minimization method and the randomisation was stratified by institution, age (20-64 vs. 65-79 years), and liver metastases (present vs. absent). The primary analysis was revised to adopt a hierarchical testing procedure; we first compare OS between the two arms in left-sided primary tumor population, and only if there is statistically significant difference, then ITT population analysis will be performed. In this revised plan, the expected number of deaths is 420 in the left-sided population to provide 80% power to detect an OS hazard ratio of 0.74 at a one-sided significance level of 0.02101 determined on the alpha spending function approach after one interim analysis. A large-scale exploratory biomarker substudy to identify potential biomarker candidates using tumor tissue and circulating tumor DNA is also underway (Clinical trial no.: NCT02394834). The data cut off for the primary analysis is expected to be during 1Q 2021. Results: Results are expected in 2021. Conclusions: Results are expected in 2021. Clinical trial information: NCT0239475.

scholarly journals Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

2021 ◽  
Vol 22 (14) ◽  
pp. 7717
Author(s):  
Guido Giordano ◽  
Pietro Parcesepe ◽  
Giuseppina Bruno ◽  
Annamaria Piscazzi ◽  
Vincenzo Lizzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Checkpoint Inhibitors ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Braf Mutations ◽  
Mutational Status ◽  
First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

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