FCγRIIa and FCγRIIIa single nucleotide polymorphisms (SNPs) and cetuximab benefit in the EXCITE trial

Abstract

Conclusions: EMT status of circulating tumor cells has a close relationship with responses to chemo-radiotherapy and tumor metastasis in rectal cancer patients. Further studies should be taken in the near future. Legal entity responsible for the study: Fudan University Shanghai Cancer Center Funding: Natural Science Foundation of China Disclosure: All authors have declared no conflicts of interest.187P Impact of KRAS mutational status and primary tumor location on the efficacy of aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer: An exploratory analysis in a phase II study

Analysis of KRAS, NRAS, BRAF, PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients

“…While this inconsistency may be secondary to the limited sample size and the relatively low number of survival events, it is also possible that the long‐term prognostic effect of TP53 could have been diluted by the inclusion of patients who were treated without cetuximab and in fact accounted for the majority of the study population. Indeed, in a previous exploratory biomarker analysis of the EXPERT‐C trial, we showed that TP53 was an independent predictive factor for PFS and OS only in the group of cetuximab‐treated patients, possibly due to a selective therapeutic effect of EGFR inhibition on micrometastatic foci of TP53 wild‐type tumours . Therefore, beyond the confirmation of reduced pathological regression of TP53 mutant tumours after neoadjuvant therapy, the findings of our analysis appear to provide further indirect support to the design of prospective trials investigating TP53 as predictive biomarker for cetuximab in LARC.…”

“…Indeed, in a previous exploratory biomarker analysis of the EXPERT-C trial, we showed that TP53 was an independent predictive factor for PFS and OS only in the group of cetuximabtreated patients, possibly due to a selective therapeutic effect of EGFR inhibition on micrometastatic foci of TP53 wild-type tumours. 20,26 Therefore, beyond the confirmation of reduced pathological regression of TP53 mutant tumours after neoadjuvant therapy, the findings of our analysis appear to provide further indirect support to the design of prospective trials investigating TP53 as predictive biomarker for cetuximab in LARC.…”

A phase 1 study of cetuximab and lapatinib in patients with advanced solid tumor malignancies

“…For cetuximab, mutations in the Kras protein—which is downstream from the EGFR receptor—can nullify the benefit from blocking the receptor, leading to persistent intracellular signaling and cellular growth. Our finding that a germline SNP in FcγRIIA correlates with clinical benefit is provocative, confirms other findings, and deserves additional exploration. The observed impact by this polymorphism is likely because of cetuximab (and not lapatinib) therapy given the drug's mechanism of action, and it may indicate different activation of antibody‐dependent cellular cytotoxicity …”