XAGE1 antibody confers survival benefits to lung adenocarcinoma patients

By Laura Cowen, medwireNews Reporter

Patients with advanced lung adenocarcinoma who produce the XAGE1 (GAGED2a) antibody appear to survive twice as long as those who do not produce it, Japanese study data show.

Eiichi Nakayama (Kawasaki University of Medical Welfare, Okayama) and colleagues explain that the cancer/testis antigen XAGE1 (GAGED2a) is expressed in approximately 40% of advanced lung adenocarcinomas, and approximately half of patients with antigen-positive tumours naturally produce the XAGE1 (GAGED2a) antibody.

To investigate the clinical relevance of the XAGE1 (GAGED2a) immune response, Nakayama and team studied 145 patients with advanced (stage IIIB/IV) lung adenocarcinoma.

Of the patients, 101 had endothelial growth factor receptor wild-type (EGFRwt) tumours, which were treated with conventional platinum-based doublet chemotherapy, while 44 had EGFR-mutated (EGFRmt) tumours and were treated with an EGFR tyrosine kinase inhibitor (TKI) and conventional chemotherapy.

Immunohistochemistry and enzyme-linked immunosorbent assay testing revealed that 33 patients expressed both the XAGE1 (GAGED2a) antigen and antibody, a further 25 were positive for the antigen only and the remaining 87 expressed neither antigen nor antibody.

Median overall survival (OS) was longest among the patients with both antigen and antibody, at 33.3 months, and was significantly longer than that among the patients with XAGE1 (GAGED2a) antigen only, at 13.7 months. Patients with neither antigen nor antibody had a median OS of 15.9 months.

Stratification of the patients by EGFR mutation status showed that the OS of the antibody-positive patients was significantly longer than that of antibody-negative patients, regardless of mutation status, at a median of 31.5 months versus 15.6 months in the EGFRwt group and 34.7 months versus 11.1 months in the EGFRmt group.

However, while OS was equally short regardless of antigen status in antibody-negative patients with EGFRwt (15.6 and 12.3 months for antigen-positive and negative, respectively), it was significantly shorter in antibody-negative patients with EGFRmt who were antigen-positive compared with those who were antigen-negative (11.1 vs 31.2 months).

Taken together, these findings indicate that the survival shortening effect of XAGE1 (GAGED2a) antigen expression is specific to EGFRmt tumours or related to EGFR-TKI treatment, say Nakayama et al.

Multivariate analysis showed that the presence of the XAGE1 (GAGED2a) antibody was a significant predictor of prolonged OS in patients with XAGE1 (GAGED2a) antigen-positive tumours (hazard ratio [HR]=0.18), and in patients with either EGFRwt (HR=0.50) or EGFRmt tumours (HR=0.17).

By contrast, XAGE1 (GAGED2a) antigen expression was associated with significantly worse OS in patients with EGFRmt tumours (HR=5.23).

“The findings suggest that production of the XAGE1 (GAGED2a) antibody predicts good prognosis for lung adenocarcinoma patients as an immune biomarker and the protective effect of this naturally occurring immune response supports the concept of immunotherapy”, Nakayama et al conclude in Clinical Cancer Research.

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