EP1.01-94 The Role of Neoadjuvant Chemo-Immunotherapy in Unresectable Non-Small Cell Lung Cancer

Current practices and guidelines invoke a limited role for neoadjuvant therapies in NSCLC. These strategies are not considered for use in advanced, unresectable disease. However, the development of immune checkpoint inhibitors has drastically improved the efficacy of systemic treatments for NSCLC. We describe the case of a patient who was diagnosed with squamous cell carcinoma of the lung. Imaging demonstrated a 7.9-cm right lower lobe lesion, a 1.8-cm satellite right middle lobe nodule, and ipsilateral mediastinal lymphadenopathy, consistent with stage IIIB disease. The tumor biopsy exhibited 5% PD-L1 positivity in tumor cells. Tissue next generation sequencing (NGS) revealed loss-of-function mutations in RB1, TP53, and EP300, copy number gain in PIK3CA, and tumor mutational burden of 4.3/Mb. Analysis of circulating tumor DNA (ctDNA) demonstrated a highest allele fraction of 4.1% (TP53 mutant clone). As the tumor was deemed unresectable, the patient was started on carboplatin, nab-paclitaxel, and pembrolizumab. Follow-up imaging at 12 weeks after 4 cycles showed partial response, with significant reduction in tumor size and improvement in lymphadenopathy. After tumor board discussion, the decision was made to proceed with surgical resection. A right thoracotomy with bilobectomy was successfully performed. Resected tumor demonstrated major pathologic response with less than 5% viable cancer cells. Whole-genome sequencing of plasma was also carried out on blood collected over the course of treatment. The observable cancer signal shrank to less than 5% of the baseline as early as 25 days after treatment start. Finally, repeat ctDNA analysis 6 weeks after the surgery showed no detectable somatic variants. Conversion of unresectable tumors in NSCLC may be more feasible with modern treatment regimens. The potential efficacy of neoadjuvant strategies using chemoimmunotherapy warrants further clinical investigation.