Prognostic value of class III b-tubulin (TUBB3) in operable non-small cell lung cancer (NSCLC) and predictive value for adjuvant cisplatin-based chemotherapy (CT): A validation study on three randomized trials

Abstract

7506 Background: The IALT and JBR.10 randomized trials both demonstrated the survival advantage of adjuvant platinum-based CT for patients with resected NSCLC. We previously showed by immunohistochemistry (IHC) that high TUBB3 expression might correlate with greater benefit from adjuvant vinorelbine/cisplatin CT in an analysis of tumor tissues from 265 patients in the JBR.10 trial. Here, we sought to verify the previous suggestions in the IALT trial. Since some CT regimens in the IALT trial did not include an anti-tubulin agent, we also tested the hypothesis that the value of TUBB3 expression in predicting benefit from CT was specific to anti-tubulin containing regimens. Methods: Tissue microarrays representing 737 patients on the IALT trial were stained for TUBB3. A score was generated based on the intensity and the proportion of positive-staining tumor cells in each case. Patients were classified as having high or low TUBB3 expression based on the median score. Correlations were assessed between TUBB3 and known prognostic factors, disease-free survival (DFS), overall survival (OS) and CT effect through stratified logistic and Cox models. Results: High TUBB3 expression significantly correlated with adenocarcinoma histology (p=0.0001), lymphatic (p=0.03) and vascular invasion (p=0.01), and DFS (HR 1.26, 95% CI 1.01–1.58, p = 0.04), with a similar trend in OS (p=0.12). There was no significant interaction seen between TUBB3 status and treatment assignment in predicting DFS (HR for CT effect in high versus low TUBB3 groups =0.92, p=0.71) or OS (HR=1.01, p=0.98), nor when the analysis was restricted to anti-tubulin containing regimens (DFS: HR=0.90, p=0.71; OS: HR=0.93, p=0.82). Conclusions: High TUBB3 expression is an adverse prognostic factor in IALT, in concordance with prior observations in JBR.10. However, unlike what was suggested in JBR.10, in IALT TUBB3 expression did not correlate with benefit from adjuvant chemotherapy. More insight into the role of TUBB3 will be given at the time of the meeting when the results of IALT together with ANITA and CALGB 9633 trials will be available. No significant financial relationships to disclose.