Abstract
Immune checkpoint inhibitor (ICI)-based immunotherapy has emerged as an effective strategy for stage III non-small cell lung cancer (NSCLC). However, predictive biomarkers of response remain limited. DNA polymerase epsilon (POLE) mutations, although rare in NSCLC, are associated with an increased tumor mutational burden and enhanced neoantigen presentation, both of which may promote immune sensitivity. A 52-year-old woman was diagnosed with stage IIIA NSCLC. Tumor programmed death-ligand 1 (PD-L1) expression was negative. Molecular profiling revealed a somatic POLE mutation (NM_006231.4 (POLE): c.1270C>G (p.Leu424Val)), without additional tumor alterations. A perioperative chemo-immunotherapy approach was implemented. After three cycles of neoadjuvant carboplatin, pemetrexed, and pembrolizumab, computed tomography (CT) scan revealed a significant response. Then, the patient underwent to curative-intent surgery. Histopathological examination demonstrated a pathological complete response (pCR). Adjuvant pembrolizumab (thirteen cycles) was administered without relevant toxicities. At 18-month follow-up, the patient remained disease-free with good performance status. In conclusion, we report the case of pCR in a POLE-mutated NSCLC patient treated with perioperative chemo-immunotherapy. Incorporating a POLE evaluation could improve the integrated decision-making process for patients with NSCLC in the perioperative setting. Prospective studies are warranted to validate this observation.