Association Between EGFR Mutation Status and Out-of-field Recurrence in Locally Advanced Unresectable Non-small Cell Lung Cancer Treated With Chemoradiotherapy and Durvalumab Consolidation

Background/Aim: The efficacy of durvalumab consolidation therapy after chemoradiotherapy (PACIFIC regimen) for patients with epidermal growth factor receptor (EGFR) mutation-positive locally advanced unresectable non-small cell lung cancer (NSCLC) remains unclear. Additionally, data on failure patterns, including in-field recurrence (IFR) and out-of-field recurrence (OFR), are limited. Patients and Methods: In this retrospective study, 83 patients with locally advanced unresectable NSCLC treated with the PACIFIC regimen were analyzed. Of them, 10 patients had tumors harboring EGFR mutations. Progression-free survival (PFS), overall survival (OS), and the cumulative incidences of IFR and OFR were evaluated. Results: The median follow-up time was 26.6 months. The 2-year PFS rate was 23% [95% confidence interval (CI)=7-78%] in the EGFR mutation-positive group and 53% (95%CI=42-66%) in the EGFR mutation-negative group (p=0.15). The 2-year cumulative incidence of OFR was significantly higher in the EGFR mutation-positive group (77%, 95% CI=49-100%) than in the EGFR mutation-negative group (26%, 95%CI=16-37%) (hazard ratio=2.90, 95%CI=1.29-6.51, p=0.01). On exploratory multivariate analysis, EGFR mutation positivity, Eastern Cooperative Oncology Group performance status 2-4, and PD-L1 expression <1% were significantly associated with OFR. No significant differences in IFR, OS, and adverse events were observed between the groups. Conclusion: Although IFR and safety profiles were comparable between the two groups, EGFR mutation positivity was associated with a higher incidence of OFR. These exploratory findings highlight the limitations of durvalumab consolidation and support the shift toward alternative systemic strategies, such as osimertinib, in patients with EGFR mutation-positive locally advanced unresectable NSCLC.