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

Autor:	Manzanares-Martin B; Immunology Unit, Reina Sofia University Hospital, Cordoba, Andalucía, Spain., Cebrián Aranda A; Oncology, Translational Oncology Division, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid, Madrid, Spain arancha.cebrian@oncohealth.eu lpuerto@oncohealth.eu jesus.garciafoncillas@oncohealth.eu., Del Puerto-Nevado L; Oncology, Translational Oncology Division, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid, Madrid, Spain arancha.cebrian@oncohealth.eu lpuerto@oncohealth.eu jesus.garciafoncillas@oncohealth.eu., González R; Immunology Unit, Reina Sofia University Hospital, Cordoba, Andalucía, Spain., Solanes S; Oncology, Translational Oncology Division, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid, Madrid, Spain., Gómez-España MA; Medical Oncology, Reina Sofia University Hospital, Cordoba, Andalucía, Spain., García-Foncillas J; Oncology, Translational Oncology Division, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid, Madrid, Spain arancha.cebrian@oncohealth.eu lpuerto@oncohealth.eu jesus.garciafoncillas@oncohealth.eu., Aranda E; Medical Oncology, Reina Sofia University Hospital, Cordoba, Andalucía, Spain.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2021 Apr; Vol. 9 (4).
DOI:	10.1136/jitc-2020-001705
Abstrakt:	Aim: 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. Methods: 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. Results: 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. Conclusions: 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. Trial Registration Number: NCT01450319, EudraCT 2010-023580-18. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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