Factors predicting the efficacy of osimertinib in t790m‐mutated metastatic lung adenocarcinoma

Background and Aims: Lung cancer ranks highest amongst cancer mortalities worldwide, with non-small cell lung cancer (NSCLC) comprising of 85% all reported cases. Most advanced stage patients are largely reliant on targeted therapies. However, EGFR-targeted therapies are only effective in patients harboring an EGFR mutation, leaving the remaining 70–90% wildtype EGFR patients with an urgently unmet medical need. The tetraspanin, CD151, is associated with poor prognosis in NSCLC, but the clinical significance of its expression and relationship with EGFR mutation status is unknown. We investigated the association between CD151 expression with EGFR mutation status in NSCLC and determined the prognostic biomarker value of this relationship. Methods: 157 adenocarcinoma patient lung biopsy sections (from 1989–2011, in Singapore), were evaluated by immunostaining for CD151 expression and then compared with patient clinicopathological parameters and survival outcome. Gene expression and clinical data from 199 wildtype EGFR patients in the TCGA lung adenocarcinoma (LUAD) cohort were analysed for further validation. Results: There is a strong association between CD151 expression and wildtype EGFR patients (P = 0.005). CD151 expression was also associated with Chinese ethnicity and TNM (tumor, node and metastasis) stage, respectively. Importantly, higher cumulative incidence of death due to disease was observed in patients with both wildtype EGFR and high CD151 expression when compared against the other subgroups (P = 0.011). In support of this, higher rate of disease-specific death was observed in the high CD151 subgroup from the TCGA LUAD cohort compared to the remaining low CD151 subgroup. Conclusion: Expression of both wildtype EGFR and high CD151 is strongly associated with poorer disease outcome compared to other NSCLC subgroups, suggesting that (1) CD151 is a prognostic biomarker which may help to further stratify wildtype EGFR subsets, and (2) CD151 as a therapeutic target in the development of novel alternative and/or complementary agents for the treatment of wildtype EGFR-NSCLC subgroups.