Specific TCR profiles predict clinical outcome of adjuvant EGFR-TKIs for resected EGFR-mutant non-small cell lung cancer.

ABSTRACT

BACKGROUND: ADJUVANT-CTONG1104 reported a favorable survival outcome from adjuvant gefitinib treatment over chemotherapy in EGFR-mutant non-small cell lung cancer (NSCLC) patients. However, heterogeneous benefit from EGFR-TKIs and chemotherapy demands further biomarker exploration for patient selection. Previously, we identified certain TCR sequences with predictive value for adjuvant therapies from the CTONG1104 trial and found a relationship between the TCR repertoire and genetic variations. It remains unknown which TCR sequences could further enhance the prediction for only adjuvant EGFR-TKI. METHODS: In this study, 57 tumor and 12 tumor-adjacent samples, respectively, from gefitinib-treated patients in the CTONG1104 were collected for TCR ß gene sequencing. We attempted to constitute a predictive model for prognosis and favorable adjuvant EGFR-TKI outcome for patients with early-stage NSCLC and EGFR mutations. RESULTS: The TCR rearrangements demonstrated significant prediction for overall survival (OS). A combined model of high frequent Vß7-3Jß2-5 and Vß24-1Jß2-1 with lower frequent Vß5-6Jß2-7 and Vß28Jß2-2 constituted the best value for predicting OS (P < 0.001; Hazard Ratio [HR] = 9.65, 95% confidence interval [CI] 2.27 to 41.12) or DFS (P = 0.02; HR = 2.61, 95% CI 1.13 to 6.03). In Cox regression analyses, when multiple clinical data were included, the risk score remained an independent prognostic predictor for OS (P = 0.003; HR = 9.49; 95% CI 2.21 to 40.92) and DFS (P = 0.015; HR = 3.13; 95% CI 1.25 to 7.87). CONCLUSIONS: In this study, a predictive model was constituted with specific TCR sequences for prognosis prediction and gefitinib benefit in the ADJUVANT-CTONG1104 trial. We provide a potential immune biomarker for EGFR-mutant NSCLC patients who might benefit from an adjuvant EGFR-TKI.