A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients

Abstract

7510 Background: The JBR.10 trial demonstrated a significant survival benefit from adjuvant chemotherapy in stage IB-II NSCLC patients (HR 0.69, p=0.04). However, a significant interaction with stage was seen, with benefit limited to stage II patients. Gene expression profiling may identify patient groups with significantly different prognosis, with potential for improved selection of patients to receive adjuvant chemotherapy. Methods: Gene expression profiling by Affymetrix U133A was performed on RNA isolated from snap-frozen banked tumor tissues of 133 (62 on observation and 71 on chemotherapy) JBR.10 patients. A minimal prognostic gene set was identified based on goodness-of-fit (R square) of the Cox proportional hazard model and leave one out cross-validation in the observation patients. Results: A 15-gene expression signature was identified that separated the 62 observation patients into groups with high (n=33) and low risk (n=29) for death (HR 60.1, p< 0.0001). This prognostic signature was validated in five independent public gene expression datasets (stage I-II patients, total n=372). Chemotherapy significantly reduced the risk of death in high-risk patients (HR 0.27, C.I. 0.14–0.51, p<0.0001). The benefit of chemotherapy was seen both in high-risk stage IB (HR 0.28, p=0.007) and stage II (HR 0.26, p=0.0059) patients, but not in low-risk patients (HR 15.49, p=0.008). Interaction of chemotherapy and expression signature was highly significant (p=0.0001). Conclusions: We have identified a 15-gene signature that is an independent prognostic marker in early stage NSCLC for identifying more selectively than stage, patients who may benefit from adjuvant chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pierre Fabre