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Association details:
| Biomarker: | KRAS mutation |
|---|---|
| Cancer: | Colorectal Cancer |
| Drug: | Erbitux (cetuximab) (EGFR inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Expanded Low Allele Frequency RAS and BRAF V600E Testing in Metastatic Colorectal Cancer as Predictive Biomarkers for Cetuximab in the Randomized CO.17 Trial
Excerpt:
CO.17 trial compared cetuximab versus best supportive care (BSC) in RAS/BRAF-unselected mCRC. 17 trial using BEAMing for KRAS/NRAS (codons 12/13/59/61/117/146) and BRAF V600E. Cetuximab did not improve OS/PFS for KRAS-, NRAS-, or BRAF-mutated tumors...
DOI:
10.1158/1078-0432.CCR-20-2710
Trial ID:
Source:
Title:
Sirolimus and Cetuximab in Advanced Malignancies
Excerpt:
......
Trial ID:
Source:
Title:
FLOX + Cetuximab (Erbitux®) for Patients With Metastatic Colorectal Cancer and Wild Type K-RAS Tumor
Excerpt:
......
Trial ID:
More C2 evidence
Source:
Title:
Cetuximab as salvage therapy in patients with neo wild-type RAS/RAF metastatic colorectal cancer. A Proof-of-concept study
Excerpt:
...Unresectable metastatic RAS mutant (either KRAS or NRAS tumor gene mutation) colorectal cancer, 5. ...
Trial ID:
Source:
Title:
Cetuximab as Salvage Therapy in Patients With Neo Wild-type RAS/RAF Metastatic Colorectal Cancer With Liver Metastases.
Excerpt:
...Unresectable metastatic RAS mutant (either KRAS or NRAS tumor gene mutation) colorectal cancer, 5....
Trial ID:
Source:
Title:
Cetuximab Rechallenge Study
Excerpt:
...- KRAS mutation status of the primary or metastastic CRC tumor must be wild-type....
Trial ID:
Source:
Title:
Cetuximab Plus Biweekly Capecitabine and Oxaliplatin in KRAS Wild Type Metastatic Colorectal Cancer
Excerpt:
...- Histologically confirmed diagnosis of advanced adenocarcinoma of the colon or rectum, with KRAS wild type on mutational analysis....
Trial ID:
Source:
Title:
AlloStim® In-Situ Vaccine in Pre-Treated Metastatic Colorectal Cancer
Excerpt:
...KRAS/BRAF mutant disease or KRAS wild type w/previous anti-EGFR treatment 5....
Trial ID:
Source:
Title:
FOLFOX Chemotherapy Regimen (5-FU, Leucovorin, Oxaliplatin) in Metastatic Colorectal Cancer
Excerpt:
...Phase II: Patient must have known KRAS (exon 1, codon 12, 13) or sufficient available tumor tissue from the primary tumor or metastatic site for KRAS mutation analysis [Phase II only]....
Trial ID:
Source:
Title:
Phase 1 and 2 Study of PX-866 and Cetuximab
Excerpt:
...- Kras mutation in codon 12 or 13 (CRC patients only)...
Trial ID:
Source:
Title:
BAY 43-9006 Plus Cetuximab to Treat Colorectal Cancer
Excerpt:
...- Tumor blocks or unstained slides from archival pathological specimen suitable for the isolation of genomic DNA (deoxyribonucleic acid) must be available to determine the status of mutations in KRAS in the tumor....
Trial ID:
Source:
Title:
Cetuximab Combined With Irinotecan in First-line Therapy for Metastatic Colorectal Cancer (CRYSTAL)
Excerpt:
...Progression-free Survival Time (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population) - Independent Review Committee (IRC) Assessments`Progression-free Survival Time (KRAS Mutant Population) - Independent Review Committee (IRC) Assessments...
Trial ID:
Source:
Title:
Irinotecan Hydrochloride With FOLFIRI and Cetuximab as First-Line Therapy in Treating Patients With RAS Wild-Type Colorectal Cancer
Excerpt:
...- RAS wild-type status (by a Clinical Laboratory Improvement Amendments [CLIA] certified assay that includes all known mutations in Kirsten rat sarcoma viral oncogene homolog [KRAS], Harvey rat sarcoma viral oncogene homolog [HRAS], and neuroblastoma RAS viral (v-ras) oncogene homolog [NRAS])...
Trial ID:
Source:
Title:
Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favorable FcγRIIa (CD32) Genotype
Excerpt:
...- Histological confirmed colorectal cancer (CRC) with mutated K-RAS and favorable genotypes (any H in FcγRIIa-131)....
Trial ID:
Source:
Title:
Irinotecan, Cetuximab and Everolimus to Patients With Metastatic Colorectal Cancer
Excerpt:
...- Patients with KRAS-mutation in their primary tumour or metastasis....
Trial ID:
Source:
Title:
Efficacy and Safety Study of Imprime PGG With Cetuximab in Subjects With Stage IV KRAS-Mutated Colorectal Cancer
Excerpt:
...Tumor has known KRAS mutation; 4....
Trial ID:
Source:
Title:
Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab and Erlotinib
Excerpt:
...Responses will be evaluated for the whole patient group and separately for k-ras wild-type and k-ras mutant tumours...
Trial ID:
Source:
Title:
PREDICTIVE MARKERS OF THE EFFICACY IN METASTATIC COLORECTAL TUMOR TREATED WITH CETUXIMAB - PHASE 2 STUDY
Excerpt:
...Assessing in patients with metastatic colorectal cancer refractory to treatment with chemotherapy and Irinotecan 5FU the correlation between the response to treatment with Cetuximab in combination with chemotherapy based Irinotecan;search for mutations of K-RAS and odetermination of PTEN by immunohistochemistry;Gene amplification dell'EGFR determined by FISH;the intensity of expression dell'EGFR determined by immunohistochemistry test with DAKO and Zymed (monoclonal antibody clone 31G7)...
Trial ID:
Source:
Title:
A study on NKTR-255 in combination with Cetuximab as salvage treatment for Solid Tumors Estudio sobre NKTR-255 en combinación con Cetuximab como tratamiento de rescate para tumores sólidos.
Excerpt:
...Los pacientes deben tener un diagnóstico de CCR avanzado confirmado histológica o citológicamente; los pacientes de la fase 2 deberán tener un CCR avanzado con expresión de EGFR y KRAS no mutado confirmado. ...
Trial ID:
Source:
Title:
A randomized phase II study of FOLFORI plus or not CETUXIMAB in elderly advanced colorectal cancer patients. Studio randomizatto di fase II con FOLFIRI piu' CETUXIMAB o FOLFIRI da solo in pazienti anziani affetti da tumore colo-rettale avanzato.
Excerpt:
...KRAS non mutato. ...
Trial ID:
Source:
Title:
A study to explore the effects of cetuximab alone or in combination with irinotecan in patients with an abnormal gene (KRAS) in their colon cancer cells.
Excerpt:
...Prior confirmation of tumour KRAS status as either KRAS WT (with no mutations or changes in BRAF, NRAS, PIK3CA exon20) OR KRAS G13D mutation,6. ...
Trial ID:
Source:
Title:
Study of JDQ443 , in combination with trametinib or ribociclib or cetuximab, in advanced cancer with a specific mutation (changes in a gene) called KRAS G12C
Excerpt:
...Dose Escalation:•Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are ineligible to receive such therapy.Phase II:•Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy•Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless patient was ineligible to such therapy.All patients:•ECOG performance status of 0 or 1.•Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution’s guidelines.`...
Trial ID:
Source:
Title:
FLOX + Erbitux. 1. line treatment to patients with metastatic colorectal cancer and wild type K-RAS tumor. A phase II study.
Excerpt:
...Histology and staging disease:• Histological proven adenocarcinoma of the colon or rectum• At least one measurable metastatic lesion according to RECIST criteria• If only one metastatic lesion, histology is mandatoryMutation level:• Tumor tissue (primary or metastasis) typological classified as K-RAS wildtype in codon 12 and 13 in exon 1 at real-time PCRGeneral conditions: • Age >18 and 18 and < 75 years • WHO performance status ≤ 2; life expectancy of more than 3 months• Adequate haematological function: (Hb ≥ 6.2 μmol/d, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L)• Adequate renal and hepatic functions: total bilirubin ≤ 1.5 upper normal limit, creatinine ≤ 1.25 × upper normal limit, ALAT ≤ 3 x upper normal limits, and ≤ 5 x upper normal limits in case of liver metastases• Written informed consent prior to inclusion must be obtained and documented according to the local regulatory requirementsOther:• Fertile patients must use adequate contraceptives...
Trial ID:
Source:
Title:
Multicenter prospective single-arm study investigating the efficacy and safety of second-line cetuximab plus chemotherapy treatment in initially RAS-mt mCRC patients who converted to RAS-wt at the time of first progression Studio di fase II a singolo braccio di terapia di II linea con cetuximab e chemioterapia in pazienti con carcinoma colorettale metastatico KRAS e NRAS mutato alla diagnosi con assenza di mutazioni di KRAS/NRAS su plasma alla progressione da prima linea
Excerpt:
...- KRAS/NRAS-wt status, tested on ctDNA, at the time of progression after first line treatment- Life expectancy of at least 3 months; • Diagnosi istologica di adenocarcinoma del colon-retto• KRAS/NRAS mutato su biopsia tissutale (tumore primitivo /metastasi) al momento della diagnosi• Evidenza radiologica di progressione di malattia dopo prima linea con chemioterapia e bevacizumab• Malattia misurabile secondo criteri RECIST (RECIST criteria, vers.1.1); • Uomo o donna, età > 18 anni • ECOG Performance Status = 2; • Adeguata funzionalità ematologica, epatica e renale valutata entro 14 giorni dall’inizio del trattamento in studio Adequate bone marrow function (without hematopoietic growth factor or transfusion support within 14 days prior to study enrollment), including:a. ...
Trial ID:
Source:
Title:
Phase Fase II examination of irinotecan, cetuximab and everolimus for patients resistente to chemoptherapy with metastatic colorectal cancer and KRAS mutation or with KRAS wildtype after progression on therapy with irinotecan og cetuximab – effect and biological markers.
Excerpt:
...Patients with KRAS mutation in their primary tumour or metastasis.5. ...
Trial ID:
Source:
Title:
A study to evaluate the efficacy and safety of SOT101 in combination with cetuximab in patients with a specific subtype of colon and/or rectum cancer Estudio para evaluar la eficacia y seguridad de SOT101 en combinación con cetuximab en pacientes con un subtipo específico de cáncer de colon y/o recto
Excerpt:
...o un laboratorio local con experiencia utilizando métodos de prueba validados para la detección de mutaciones de K-RAS y N-RAS (exones 2, 3 y 4).6. ...
Trial ID:
Source:
Title:
Randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer (CRC) with either KRAS WT or G13D mutation.
Excerpt:
...“All RAS WT”, - that is no mutation or changes in either KRAS NRAS...
Trial ID:
Source:
Title:
A study evaluating the efficacy of cetuximab in combination with FOLFIRI in patients with metastatic colorectal cancer after positive genetic testing of cancer cells Eine Studie zur Überprüfung der Wirksamkeit von Cetuximab in Kombination mit FOLFIRI bei Patienten mit metastasiertem Darmkrebs nach erfolgter positiver genetischer Untersuchung der Krebszellen
Excerpt:
...• Histologically confirmed, UICC stage IV adenocarcinoma of the left-sided colon or rectum with metastases (metastatic colorectal cancer), primarily non-resectable, confirmed RAS mutations proven in the primary tumor or metastasis (KRAS and NRAS exon 2, 3, 4)• Age ≥ 18 years on day of signing informed consent• No previous chemotherapy for metastatic disease (1- 2 cycles FOLFIRI or mFOLFIRI are permitted before enrolment until RAS status is determined)• Patients suitable for chemotherapy administration• ECOG performance status 0-1• Consent to liquid biopsy and mutation analysis• Estimated life expectancy > 3 months• Presence of at least one measurable reference lesion according to the RECIST 1.1 criteria (chest CT and abdominal CT 4 weeks or less before enrollment)• Adequate bone marrow function defined as:o Leukocytes 3.0 x 109/L with neutrophils 1.5 x 109/Lo Thrombocytes 100 x 109/Lo Hemoglobin 9 g/dL• Adequate hepatic function defined as:o Serum bilirubin 1.5 x ULNo ALAT and ASAT 2.5 x ULN (in the presence of hepatic metastases, ALAT and ASAT 5 x ULN)• Adequate renal function: Creatinine clearance 50 mL/min• Adequate cardiac function defined aso Normal ECG and echocardiogram with a left ventricular ejection fraction (LVEF) of 55%• INR < 1.5 and aPTT < 1.5 x ULN (patients without anticoagulation). ...
Trial ID:
Source:
Title:
Clinical trial in patients with metastatic colorectal Cancer to evaluate the response of removable liver metastases after treatment with Cetuximab (Erbitux). Ensayo Clínico en pacientes con Cancer colorectal metastásico para evaluar la respuesta de las metástasis de hígado extraíbles tras recibir tratamiento con Cetuximab (Erbitux).
Excerpt:
...1.Hombre o mujer >= 18 años.2.Capaz de comprender, firmar y fechar un formulario de consentimiento informado aprobado por el CEIC.3.Cáncer colorrectal metastásico confirmado histológicamente o citológicamente por el investigador.4.Cáncer colorrectal KRAS no mutado (determinado en el tumor primario) con metástasis hepáticas limitadas al hígado, resecables o potencialmente resecables, decidido en el seno del Comité Multidisciplinar. ...
Trial ID:
Source:
Title:
RAS Switch in Patients With Metastatic RAS Native Colorectal Tumors Treated With 1st Line FOLFIRI-Cetuximab
Excerpt:
...To estimate the proportion of patients with advanced colorectal cancer in whom KRAS mutation can be detected in circulating extracellular DNA...
Trial ID:
Source:
Title:
Cetuximab Plus Irinotecan in Colorectal Cancer Patients Who Progressed After Failure With Cetuximab Plus Irinotecan
Excerpt:
...- Patient must have tumor tissue tested for KRAS mutation and should be confirmed to carry a wild type...
Trial ID:
Source:
Title:
Study to investigate JAB-21822 Monotherapy and Combination Therapy in Adult Patients with Advanced Solid Tumors Harboring KRAS G12C Mutation Estudio para evaluar JAB-21822 en monoterapia y en combinación en pacientes adultos con tumores sólidos avanzados portadores de la mutación KRAS G12C
Excerpt:
...-Written ICF must be signed and dated by the participant prior to the performance of any study-specific procedures, sampling, or analyses.-≥18 years of age at the time of signing the ICF.-ECOG performance status score of 0 or 1.-Life expectancy ≥3 months.-Participant must be able to provide an archived tumor sample or tumor tissue from a newly obtained biopsy from the tumor site which has not been previously irradiated.-Histologically or cytologically confirmed solid tumors with KRAS G12C mutation by laboratories, which are either CLIA certified or recognized by local institution, and meets the following criteria:Phase 1; Cohort A0a.Have histologically or cytologically confirmed metastatic or locally advancedsolid tumor that is not a candidate for curative intervention.b.Must have received at least 1 prior standard therapy for their tumor type and stage.Phase 2; Cohort A1, A2 and Cohort B1, B2A1:a.Has histologically or cytologically confirmed diagnosis of unresectable StageIIIB or Stage IV NSCLC and is not a candidate for curative intervention.b.Must have received a platinum-based therapy and an immune checkpointinhibitor unless such therapies are contraindicated or not available to the participant or the participant refused them. ...
Trial ID:
Source:
Title:
Oxaliplatin and Cetuximab in First-line Treatment of Metastatic Colorectal Cancer (mCRC)
Excerpt:
...Best Overall Response Rate (Chinese V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Wild-Type Population)`Best Overall Response Rate (KRAS Mutant Population)`Progression-free Survival Time`Progression-free Survival Time (KRAS Wild-Type Population)`Progression-free Survival Time (KRAS Mutant Population)`Overall Survival Time`Overall Survival Time (KRAS Wild-Type Population)`Overall Survival Time (KRAS Mutant Population)`Participants With No Residual Tumor After Metastatic Surgery`Disease Control Rate (Cut Off Date 4 August 2006)`Duration of Response`Safety - Number of Patients Experiencing Any Adverse Event...
Trial ID:
Source:
Title:
Cetuximab and Simvastatin in Treating Patients With Advanced or Metastatic Colorectal Cancer
Excerpt:
...- Failed prior oxaliplatin-, fluorouracil (5-FU)-, and irinotecan-containing regimens AND have the presence of a k-ras mutation within codon 12, 13, or 61...
Trial ID:
Source:
Title:
Neoadjuvant FOLFOX6 + Cetuximab in Patients With Colorectal Cancer and Unresectable Liver Metastasis
Excerpt:
...Response rate (according to RECIST)`Progression-free survival time`Overall survival timeToxicity profile (according to NCI CTCAE v3)`Correlative analyses between pretreatment EGFR, KRAS mutation and response rate/survival...
Trial ID:
Source:
Title:
A Study to Assess the Efficacy and Safety of Lenalidomide in Combination With Cetuximab in Pre-treated Patients With KRAS Mutant Colorectal Cancer
Excerpt:
...Confirmed K-RAS mutant tumor 3....
Trial ID:
Source:
Title:
Safety and Efficacy Study of Combination Therapy With Cetuximab and FOLFOX4 in Patients With Colorectal Cancer
Excerpt:
...Determine safety of combination, surgical resectability and R0 resections, clinical benefit, time to disease progression, time to onset of response, duration of response, time to treatment failure, overall survival time`determination of polymorphisms of the intron 1 of the EGFR gene, TS, XRCC1, XPD, serum levels of EGFR and ATP7A and ATP7B, nº of copies of EGFR gene, the levels of PTEN, EGFR, AKT y MAPK proteins, and mutations at EGFR, PI3KCA, K-RAS y B-RAF genes...
Trial ID:
Source:
Title:
Lenalidomide and Cetuximab in Treating Patients With Metastatic Colorectal Cancer
Excerpt:
...Time to progression of disease`Tumor response according to RECIST`Lab correlatives (FCGRIIa and FCGRIIIa polymorphisms, K-Ras and B-Raf mutations)...
Trial ID:
Source:
Title:
Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
Excerpt:
...Disease-free Survival (Arms A and D: Mutant KRAS Patients)`Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Wild-type KRAS Patients)`Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Mutant KRAS Patients)`Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Wild-type KRAS Patients)`Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Mutant KRAS Patients)...
Trial ID:
Source:
Title:
Cetuximab in Third Line for Mutant APC, TP53 and RAS Patients With Refractory Metastatic Colorectal Cancer
Excerpt:
...- Histologically confirmed metastatic colorectal adenocarcinoma with mutant APC, TP53 and KRAS genes as determined by the local CLIA-certified laboratory are eligible....
Trial ID:
Source:
Title:
MoLiMoR - A Study With FOLFIRI-based First-line Therapy With or Without Intermittent Cetuximab
Excerpt:
...- Histologically confirmed, UICC stage IV adenocarcinoma of the left-sided colon or rectum with metastases (metastatic colorectal cancer), primarily non-resectable, confirmed RAS mutations proven in the primary tumor or metastasis (KRAS ans NRAS exon 2, 3, 4)...
Trial ID:
Less C2 evidence
Source:
Title:
Chemotherapy (doublet or triplet) plus targeted therapy by RAS status as conversion therapy in colorectal cancer patients with initially unresectable liver-only metastases. The UNICANCER PRODIGE-14 randomised clinical trial
Published date:
01/06/2022
Excerpt:
PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.
Secondary therapy:
FOLFIRINOX
DOI:
10.1038/s41416-021-01644-y
Source:
Title:
Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer
Published date:
09/14/2021
Excerpt:
CONTRADICTING EVIDENCE:...Tspan6-positive patients with tumors in the proximal colon (right-sided) and those with KRAS mutations had a better response to Cetuximab than the patients that expressed low Tspan6 levels.
DOI:
https://doi.org/10.1073/pnas.2011411118
Source:
Title:
O-6 Gene alterations in ctDNA related to the resistance mechanism of anti-EGFR antibodies and clinical efficacy outcomes of anti-EGFR antibody rechallenge plus trifluridine/tipiracil in metastatic colorectal cancer patients in WJOG8916G trial
Published date:
07/04/2021
Excerpt:
...We conducted a phase II trial (WJOG8916G) to evaluate the efficacy and safety of the combination of trifluridine/tipiracil and cetuximab rechallenge in patients (pts) with metastatic colorectal cancer (mCRC)…RAS, BRAF, and PIK3CA muts in ctDNA were associated with worse clinical efficacy outcomes in mCRC patients receiving anti-EGFR antibody rechallenge plus trifluridine/tipiracil.
Secondary therapy:
trifluridine/tipiracil
DOI:
https://doi.org/10.1016/j.annonc.2021.05.010
Source:
Title:
Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
Excerpt:
Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6/10) of the cases.
DOI:
10.1038/nature11156
Source:
Title:
FOLFOX4 Plus Cetuximab for Patients With Previously Untreated Metastatic Colorectal Cancer According to Tumor RAS and BRAF Mutation Status: Updated Analysis of the CECOG/CORE 1.2.002 Study
Excerpt:
Compared with patients with RAS wt/BRAF wt tumors (n = 124; median overall survival, 28.5 months), those with RAS mutations (n = 10; median, 16.3 months; hazard ratio, 0.43; 95% confidence interval, 0.20-0.89; P = .020) or BRAF mutations (n = 14; median, 11.7 months; hazard ratio, 0.23; 95% confidence interval, 0.12-0.41; P < .0001) had worse overall survival, which remained significant (P < .04) when adjusting for differences in baseline characteristics among the mutation subgroups.
Secondary therapy:
FOLFOX4
DOI:
10.1016/j.clcc.2014.12.003
Source:
Title:
Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis
Excerpt:
KRAS mutants did not derive benefit compared with wild types, with a response rate of 6.7% (17/253) versus 35.8% (126/352; odds ratio [OR] 0.13, 95% CI 0.07-0.22; p<0.0001), a median PFS of 12 weeks versus 24 weeks (hazard ratio [HR] 1.98, 1.66-2.36; p<0.0001), and a median overall survival of 32 weeks versus 50 weeks (1.75, 1.47-2.09; p<0.0001).
DOI:
10.1016/S1470-2045(10)70130-3
Source:
Title:
Oncogenic Activation of the RAS/RAF Signaling Pathway Impairs the Response of Metastatic Colorectal Cancers to Anti–Epidermal Growth Factor Receptor Antibody Therapies
Excerpt:
RAS/RAF mutations are negatively associated with response to cetuximab or panitumumab...The presence of K-RAS mutations was not significantly linked to objective response to therapy, with a trend toward a negative association with response (1 of 11 mutations versus 15 of 37 mutations for responders versus nonresponders; P = 0.073).
DOI:
10.1158/0008-5472.CAN-06-4158
Source:
Title:
Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients
Excerpt:
In contrast, BRAF mutations (0% for responders vs. 26.1% for non-responders, p = 0.0044) and KRAS (0% for responders vs. 21.7% for non-responders, p = 0.0117) were observed exclusively in non-responders. Three of the 4 subjects with NRAS mutations were non-responders (p = 0.3053) while both PTEN mutations were detected in responders (p = 0.4993). Collective mutation frequencies of KRAS, NRAS, and BRAF combined were higher in non-responders (p = 0.0001).
DOI:
10.18632/oncotarget.8076
Source:
Title:
The First-in-class Anti-EGFR Antibody Mixture Sym004 Overcomes Cetuximab Resistance Mediated by EGFR Extracellular Domain Mutations in Colorectal Cancer
Excerpt:
Acquired resistance to cetuximab was associated with the emergence of mutations, which occurred mainly in KRAS, NRAS, and EGFR genes (Table 2).
DOI:
10.1158/1078-0432.CCR-15-2400
Source:
Title:
Activating KRAS Mutations and Overexpression of Epidermal Growth Factor Receptor as Independent Predictors in Metastatic Colorectal Cancer Patients Treated With Cetuximab
Excerpt:
Furthermore, patients with nonactivating KRAS mutants in tumors had a significantly better PFS and OS than patients with activating KRAS mutants (both P < 0.05).
DOI:
10.1097/SLA.0b013e3181bc9d96
Source:
Title:
K-ras mutations and benefit from cetuximab in advanced colorectal cancer
Excerpt:
The effect of cetuximab on overall survival was significantly greater among the patients with wild-type K-ras tumors than among those with mutated K-ras tumors (P=0.01 for the interaction between K-ras–mutation status and the assigned treatment)...The effect of cetuximab on progression-free survival was significantly greater among the patients with wild-type K-ras tumors than among those with mutated K-ras tumors...
DOI:
10.1056/NEJMoa0804385.
Trial ID:
Source:
Title:
A Molecularly Annotated Platform of Patient-Derived Xenografts (“Xenopatients”) Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer
Excerpt:
At the 6-week time point, disease stabilization changed to tumor shrinkage in 3 cases and developed into disease progression in 7 cases....Our results prospectively validated observations in patients: none of the 7 NRAS- and 3 BRAF-mutant cases (10.6% and 4.5%, respectively) or the 4 cases with KRAS rare mutations (6.1%) responded to cetuximab with tumor shrinkage or stabilization.
DOI:
10.1158/2159-8290.CD-11-0109
Source:
Title:
KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer
Excerpt:
A KRAS mutation was found in 13 tumors (43%) and was significantly associated with the absence of response to cetuximab (KRAS mutation in 0% of the 11 responder patients versus 68.4% of the 19 nonresponder patients; P = 0.0003). The overall survival of patients without KRAS mutation in their tumor was significantly higher compared with those patients with a mutated tumor (P = 0.016; median, 16.3 versus 6.9 months).
DOI:
10.1158/0008-5472.CAN-06-0191
Source:
Title:
Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer
Excerpt:
Among 92 patients treated using chemotherapy and cetuximab as salvage therapy, KRAS mutation was associated with lack of response (P=0.002) and shorter PFS (P=0.09). BRAF (P=0.0005) and PIK3CA (P=0.01) mutations also predicted reduced PFS in response to cetuximab salvage therapy.
DOI:
10.1038/sj.bjc.6605164
Source:
Title:
PIK3CA Mutations in Colorectal Cancer Are Associated with Clinical Resistance to EGFR-Targeted Monoclonal Antibodies
Excerpt:
PIK3CA mutations were significantly associated with clinical resistance to panitumumab or cetuximab; none of the mutated patients achieved objective response (P = 0.038)...Patients with PIK3CA mutations displayed a worse clinical outcome also in terms of progression-free survival (P = 0.035).
DOI:
10.1158/0008-5472.CAN-08-2466
Source:
Title:
KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab
Excerpt:
A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026).
DOI:
10.1200/JCO.2007.12.5906
Source:
Title:
PTEN Expression and KRAS Mutations on Primary Tumors and Metastases in the Prediction of Benefit From Cetuximab Plus Irinotecan for Patients With Metastatic Colorectal Cancer
Excerpt:
KRAS was mutated in 35 (40%) of 88 available primary tumors. Only two (6%) of 35 responders were found in this group compared with 13 (25%) of 53 that had KRAS wild type (OR, 0.186; 95% CI, 0.039 to 0.886; P = .024)...Patients with KRAS wild-type tumors had significantly longer mPFS and mOS than those with KRAS mutated tumors (mPFS: 4.2 v 3.1 months; HR, 0.45; 95% CI, 0.27 to 0.74; P = .003; mOS: 13.5 v 6.1 months; HR, 0.45; 95% CI, 0.22 to 0.65; P = .0004).
DOI:
10.1200/JCO.2008.20.2796
Source:
Title:
Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer
Excerpt:
KRAS mutations were present in 30% of the patients and were associated with resistance to cetuximab or panitumumab (P = .011)
DOI:
10.1200/JCO.2008.18.0786
Source:
Title:
Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer
Excerpt:
Conversely, for patients with tumor KRAS mutations, the response rate for cetuximab plus FOLFOX-4 was lower, compared with FOLFOX-4 alone (33% v 49%; OR = 0.51; 95% CI, 0.22 to 1.15; ECOG PS–adjusted CMH test, P = .106).
Secondary therapy:
FOLFOX4
DOI:
10.1200/JCO.2008.20.8397
Source:
Title:
Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR
Excerpt:
Tissue KRAS/NRAS wild-type mCRC patients were enrolled and treated with first-line cetuximab-containing chemotherapy….Among 93 patients, 84 (90.3%) had at least 1 somatic mutation in baseline ctDNA samples (average 2.74). Five patients with KRAS or NRAS hotspot mutation in the ctDNA showed significantly worse progression-free survival (PFS) (p = 0.029).
Secondary therapy:
Chemotherapy
DOI:
10.1038/s41598-021-95345-4
Source:
Title:
Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study
Excerpt:
Conversely, patients whose tumors carried mutations in KRAS who received cetuximab plus FOLFOX-4 had a decreased odds of response (34% versus 53%; odds ratio 0.459, P = 0.0290) and a higher risk of disease progression (median PFS time 5.5 versus 8.6 months; HR 1.720, P = 0.0153) compared with those who received FOLFOX-4 alone.
DOI:
10.1093/annonc/mdq632
Source:
Title:
Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab
Excerpt:
In vitro, using poly-D-lysine/laminin plates, KRAS mutant cell lines were resistant to cetuximab, whereas KRAS wild-type lines showed sensitivity to cetuximab...KRAS mutant xenografts showed resistance to cetuximab therapy, whereas KRAS wild type demonstrated an antitumor response when treated with cetuximab.
DOI:
10.1038/onc.2010.430
