RT Journal Article
T1 Improving selection of patients with metastatic colorectal cancer to benefit from cetuximab based on KIR genotypes.
A1 Manzanares-Martin, Barbara
A1 Cebrián Aranda, Arancha
A1 Del Puerto-Nevado, Laura
A1 González, Rafael
A1 Solanes, Sonia
A1 Gómez-España, Maria Auxiliadora
A1 García-Foncillas, Jesús
A1 Aranda, Enrique
K1 antibodies
K1 biomarkers
K1 natural killer t-cells
K1 neoplasm
K1 translational medical research
K1 tumor
AB Cetuximab 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. We 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. We 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. Selection 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. NCT01450319, EudraCT 2010-023580-18.
YR 2021
FD 2021
LK http://hdl.handle.net/10668/17550
UL http://hdl.handle.net/10668/17550
LA en
DS RISalud
RD Apr 11, 2025