Improving selection of patients with metastatic colorectal cancer to benefit from cetuximab based on KIR genotypes

Autor: Sonia Solanes, Enrique Aranda, Arancha Cebrián Aranda, Maria Auxiliadora Gómez-España, Jesús García-Foncillas, Barbara Manzanares-Martin, Laura del Puerto-Nevado, Rafael González
Rok vydání: 2021
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
Colorectal cancer
Cetuximab
medicine.disease_cause
0302 clinical medicine
Antineoplastic Agents
Immunological
Receptors
KIR
Risk Factors
Genotype
Immunotherapy Biomarkers
Immunology and Allergy
Neoplasm
antibodies
Neoplasm Metastasis
Child
RC254-282
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Middle Aged
Progression-Free Survival
Phenotype
030220 oncology & carcinogenesis
Child
Preschool
translational medical research
Molecular Medicine
Female
KRAS
Colorectal Neoplasms
medicine.drug
Adult
medicine.medical_specialty
tumor
Adolescent
Immunology
Clinical Decision-Making
Risk Assessment
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
Young Adult
Predictive Value of Tests
Internal medicine
medicine
Biomarkers
Tumor
Humans
Genetic Predisposition to Disease
Genotyping
neoplasms
Aged
Pharmacology
business.industry
Patient Selection
Haplotype
biomarkers
medicine.disease
digestive system diseases
Clinical trial
030104 developmental biology
Haplotypes
Spain
Mutation
natural killer t-cells
business
neoplasm
Zdroj: Journal for Immunotherapy of Cancer
Journal for ImmunoTherapy of Cancer, Vol 9, Iss 4 (2021)
ISSN: 2051-1426
Popis: AimCetuximab is a standard-of-care treatment for KRAS wild-type metastatic colorectal cancer (mCRC), but it may also be effective in a subgroup of KRAS mutant patients by its immunomodulatory activity. Here, we explore if KIR (killer cell immunoglobulin-like receptor) genotyping can provide a significant added value in the clinical outcome of patients with KRAS mutant mCRC based on cetuximab treatment.MethodsWe included 69 patients with histologically confirmed mCRC and KRAS mutation, positive EGFR expression, and Eastern Cooperative Oncology Group performance status ≤2. Based on KIR gene content, haplotype (A or B) was defined and genotypes (AA or Bx) were grouped for each patient.ResultsWe demonstrated with new evidence the immunomodulatory activity of cetuximab in patients with KRAS mutant mCRC. Patients with homozygous genotypes (AA or BB) showed shorter 12-month progression-free survival (PFS12) and poorer overall survival (OS) than those with heterozygotes (AB). Moreover, multivariate analysis confirmed stratification of patients based on genotype was an independent marker of PFS12 (HR 2.16) and the centromeric and telomeric distribution of KIRs was an independent predictor of both PFS12 (HR 2.26) and OS (HR 1.93) in patients with mCRC with KRAS mutation treated with cetuximab.ConclusionsSelection of patients with mCRC based on their KIR genotypes opens a therapeutic opportunity for patients with KRAS mutation, and it should be tested in clinical trials in comparison with other alternatives with scarce benefit.Trial registration numberNCT01450319, EudraCT 2010-023580-18.
Databáze: OpenAIRE
Externí odkaz: