Abstract
OBJECTIVES: Safety and immunologic priming using neoadjuvant, intratumoral gene-mediated cytotoxic immunotherapy (GMCI) has been established in a phase 1 clinical trial involving patients with resectable non-small cell lung cancer (NSCLC). Here we examine long-term clinical outcomes of this cohort and compare the results with a comparable contemporaneous control group. METHODS: We performed a retrospective review of a prospective database involving our trial cohort. We then identified comparable patients in a ratio of 5:1 considering pathologic stage, histology, resection extent, and age. Kaplan-Meier curves were generated. Differences in disease-free and overall survival were measured by log-rank test. RESULTS: Intratumoral GMCI was delivered to 12 patients with NSCLC by endobronchial ultrasound (n = 11) or video-assisted thoracic surgery (n = 1). Among patients receiving GMCI and control patients, more than 70% had stage II or stage III disease. Median follow-up for the surviving patients enrolled was 6.0 years (interquartile range, 5.2-6.7 years). Median diseases-free survival was significantly increased among patients receiving GMCI relative to control (2.4 years vs 1.0 year; P = .04). Median OS in the GMCI group was not reached (8 of 12 patients remain alive) versus 3.0 years in controls and was significant by log-rank at 2-7 years (P = .013-.035). CONCLUSIONS: Neoadjuvant immune stimulation induces local and systemic immune activation, is safe when combined with modern systemic therapies, and may confer long-term oncologic advantages. These data provide a foundation for additional trials exploring intratumoral immunotherapy for patients with NSCLC, especially in conjunction with immune checkpoint inhibitors.