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Association details:
Biomarker:BRAF mutation
Cancer:Colorectal Cancer
Drug:Vectibix (panitumumab) (EGFR inhibitor)
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
Title:

Anti-EGFR Therapy Rechallenge in Combination With Chemotherapy in Patients With Advanced Colorectal Cancer

Excerpt:
...Mutations analysis on platelet-resorbed tumour RNA (with Real-time PCR) in Codon 12 of KRAS gene mutations`Mutations analysis on platelet-resorbed tumour RNA (with Real-time PCR) in Codon 61 of KRAS gene mutations`Mutations analysis on platelet-resorbed tumour RNA (with Real-time PCR) in exon 15 of BRAF gene mutations`Mutations analysis on platelet-resorbed tumour RNA (with Real-time PCR) in Codon 12 of NRAS gene mutations`Mutations analysis on platelet-resorbed tumour RNA (with Real-time PCR) in Codon 61 of NRAS gene mutations`Mutations analysis on platelet-resorbed tumour RNA (with Real-time PCR) in exon 20 of PIK3CA gene mutations...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
Title:

The purpose of this clinical research is to compare two different treatments to assess whether the use of a single chemotherapy (5-FU) in combination with panitumumab may provide better results in terms of safety and efficacy compared to treatment with two chemotherapy drugs (5 -fluorouracile and oxaliplatin) in combination with panitumumab as first-line therapy in elderly patients (aged =70 years) with cancer without mutations of RAS and BRAF. Lo scopo di questa ricerca clinica è confrontare due diversi trattamenti per valutare se l’utilizzo di un solo chemioterapico (5-fluorouracile) in associazione a panitumumab possa fornire risultati migliori in termini di tollerabilità ed efficacia rispetto ad un trattamento con due farmaci chemioterapici (5-fluorouracile e oxaliplatino) in associazione a panitumumab come terapia di prima linea nei pazienti anziani (età =70 anni) con neoplasia senza mutazioni dei geni RAS e BRAF.

Excerpt:
...ECOG PS 1 or 2 for patients aged 70 to 75 years; ECOG PS 0 or 1 for patients aged > 75 years.Life expectancy of at least 12 weeks.Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse.RAS and BRAF status wild-type of primary colorectal cancer or related metastasis, centrally assessed.Neutrophils =1.5 x 109/L, Platelets =100 x 109/L, Hgb =9 g/dl.Total bilirubin =1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) =2.5 x UNL (or confermata istologicamente di adenocarcinoma del colon-rettaleMalattia metastatica inizialmente non resecabile e non precedentemente trattata con chemioterapia;Almeno una lesione misurabile secondo i criteri RECIST 1.1;Disponibilità di campione tissutale di tumore primitivo e/o metastasi;Età =70 anni;ECOG PS 1 o 2 se età compresa tra 70 e 75 anni, ECOG PS 0 o 1 se >75 anni;Aspettativa di vita di almeno 12 settimaneUna precedente chemioterapia adiuvante con fluoropirimidine in monoterapia è permessa se sono trascorsi almeno 6 mesi tra la fine dell’adiuvante e la prima recidiva;Stato mutazionale wild-type di RAS e BRAF sul tumore primitivo o sulla metastasi valutato centralmente;Neutrofili >1.5 x 109/L, Piastrine >100 x 109/L, Emoglobina >9 g/dl;Bilirubina totale 50 mL/min o creatinina sierica 1.5 x UNL;I soggetti maschili con partner fertili devono accettare l’uso di un adeguato metodo contraccettivo approvato dallo sperimentatore (es. ...
Less C2 evidence
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Evaluation of Emergent Mutations in Circulating Cell-Free DNA and Clinical Outcomes in Patients with Metastatic Colorectal Cancer Treated with Panitumumab in the ASPECCT Study

Published date:
11/28/2018
Excerpt:
Overall, 261 patients in the panitumumab arm had evaluable plasma samples….The objective response rate (complete or partial response) was 10.8% for patients with baseline RAS mutations and 21.7% for those with BRAF mutations.
DOI:
10.1158/1078-0432.CCR-18-2072
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis

Excerpt:
Conflicting evidence: Overall, the addition of C or P treatment in the BRAF-mut subgroup did not significantly improve PFS (HR, 0.88; 95% confidence interval (CI), 0.67-1.14; p=0.33), OS (HR, 0.91; 95% CI, 0.62-1.34; p=0.63) and ORR (relative risk, 1.31; 95% CI 0.83-2.08, p=0.25) compared with control regimens.
DOI:
https://doi.org/10.1016/j.ejca.2015.01.054
Evidence Level:
Sensitive: C3 – Early Trials
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...BRAF mutations alone were also not significantly associated with objective response to therapy (P = 0.312). Importantly, however, the presence of K-RAS and/or BRAF mutations was negatively associated with partial response (P = 0.005) and the logistic regression confirmed this association (odds ratio, 0.071; 95% confidence interval, 0.08–0.619; P = 0.017).
DOI:
10.1158/0008-5472.CAN-06-4158
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer

Excerpt:
BRAF mutations were associated with reduced overall survival among patients without KRAS mutations in exon 2 and among those with NRAS mutations in exon 3.
DOI:
10.1056/NEJMoa1305275
Trial ID: