Durvalumab consolidation after chemoradiotherapy (the PACIFIC regimen) improves outcomes for many patients with locally advanced unresectable non‑small cell lung cancer (NSCLC), but its efficacy in tumors harboring EGFR mutations is unclear. The study evaluated whether EGFR mutation status is associated with different failure patterns, specifically in‑field recurrence (IFR) versus out‑of‑field recurrence (OFR), in patients receiving chemoradiotherapy followed by durvalumab.
This retrospective analysis included 83 patients with locally advanced unresectable NSCLC treated with concurrent chemoradiotherapy followed by durvalumab consolidation. Among these patients, 10 had tumors positive for EGFR mutations. The study assessed progression‑free survival (PFS), overall survival (OS), and cumulative incidences of IFR and OFR. Exploratory multivariate analyses were performed to identify factors associated with OFR.
Median follow‑up for the cohort was 26.6 months. The 2‑year PFS rate in the EGFR mutation‑positive subgroup was 23% (95% confidence interval [CI] = 7–78%), compared with 53% (95% CI = 42–66%) in the EGFR‑negative subgroup; this difference did not reach statistical significance (p = 0.15). No significant difference in OS between EGFR mutation‑positive and EGFR mutation‑negative groups was reported in the abstract.
A key finding was a markedly higher cumulative incidence of out‑of‑field recurrence (OFR) at 2 years among patients with EGFR‑mutant tumors. The 2‑year OFR incidence was 77% (95% CI = 49–100%) in the EGFR mutation‑positive group versus 26% (95% CI = 16–37%) in the EGFR mutation‑negative group. The hazard ratio for OFR associated with EGFR mutation positivity was 2.90 (95% CI = 1.29–6.51) with a p value of 0.01. In contrast, rates of in‑field recurrence (IFR) were not significantly different between groups according to the abstract.
On exploratory multivariate analysis, three factors were significantly associated with increased risk of OFR: EGFR mutation positivity, Eastern Cooperative Oncology Group (ECOG) performance status of 2–4, and PD‑L1 expression <1%. The abstract does not provide full model coefficients, variable selection procedures, or additional covariates entered into the multivariate model.
The study reports no significant differences between EGFR mutation‑positive and EGFR mutation‑negative groups for IFR, OS, or adverse events. Safety profiles during durvalumab consolidation were described as comparable between the groups in the abstract.
These results suggest that while durvalumab consolidation after definitive chemoradiotherapy provides comparable in‑field control and a similar safety profile regardless of EGFR mutation status, patients with EGFR‑mutant disease experienced a substantially higher rate of distant (out‑of‑field) failure. The authors state that these exploratory findings highlight limitations of durvalumab consolidation in EGFR mutation‑positive locally advanced unresectable NSCLC and support consideration of alternative systemic strategies, such as targeted therapy with osimertinib, for this subgroup.
The source abstract describes a retrospective cohort of 83 patients with only 10 patients in the EGFR mutation‑positive subgroup. Details such as the full statistical methods, center(s) involved, selection criteria, timing of EGFR and PD‑L1 testing, subsequent systemic therapies after progression, and comprehensive limitations were not reported in the abstract.
In this retrospective analysis of patients with locally advanced unresectable NSCLC treated with chemoradiotherapy followed by durvalumab consolidation, EGFR mutation positivity was associated with a significantly higher cumulative incidence of out‑of‑field recurrence despite similar in‑field control and safety outcomes. These findings, as reported in the abstract, indicate that durvalumab consolidation may have limited impact on preventing distant progression in EGFR‑mutant disease and that alternative or additional systemic approaches merit consideration. Further prospective data and more detailed reporting are needed to define optimal consolidation strategies for EGFR mutation‑positive patients.