Association Between EGFR Mutation Status and Out-of-field Recurrence in Locally Advanced Unresectable Non-small Cell...

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.

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.

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.

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.