Brief report: durvalumab after chemoradiotherapy in unresectable stage III EGFR-mutant NSCLC: a post-hoc subgroup analysis from PACIFIC

Abstract

Introduction: Consolidation durvalumab (the 'PACIFIC regimen') is standard of care for patients with unresectable stage III NSCLC who have not progressed following chemoradiotherapy (CRT), based on data from the phase 3 placebo-controlled PACIFIC study (NCT02125461). However, the benefit of immunotherapy in patients with stage III EGFR-mutant (EGFRm) NSCLC is not well characterized. Here, we report a post-hoc exploratory efficacy and safety analysis from a subgroup of patients with EGFRm NSCLC from PACIFIC. Methods: Patients with stage III unresectable NSCLC and no progression after ≥2 cycles of platinum-based concurrent CRT were randomized (2:1) to receive durvalumab (10 mg/kg intravenously every 2 weeks, for up to 1 year) or placebo; stratified by age, sex and smoking history. Enrollment was not restricted by oncogenic driver gene mutation status or PD-L1 expression. Patients with NSCLC with an EGFR mutation, determined by local testing only, were included in this subgroup analysis. The primary endpoints were progression-free survival (PFS; assessed by blinded independent central review) and overall survival (OS). Secondary endpoints included objective response rate and safety. Statistical analyses for the subgroup of patients with EGFRm NSCLC were post-hoc and considered exploratory. Results: Of 713 patients randomized, 35 had locally confirmed EGFRm NSCLC (durvalumab, n = 24; placebo, n = 11). At data cut-off (January 11, 2021), median duration of follow-up for survival was 42.7 months (range: 3.7-74.3) for all randomized patients in the subgroup. Median PFS was 11.2 months (95% confidence interval [CI]: 7.3-20.7) with durvalumab versus 10.9 months (95% CI: 1.9-‍not evaluable [NE]) with placebo; hazard ratio [HR], 0.91 (95% CI: 0.39-2.13). Median OS was 46.8 months (95% CI: 29.9-NE) with durvalumab versus 43.0 months (95% CI: 14.9-‍NE) with placebo; HR, 1.02 (95% CI: 0.39-2.63). The safety profile of durvalumab was generally consistent with the overall population and known profile for durvalumab. Conclusions: PFS and OS outcomes with durvalumab were similar to placebo for patients with EGFRm tumors, with wide CIs. These data should be interpreted with caution due to small patient numbers and lack of a prospective study that evaluates clinical outcomes by tumor biomarker status. Further research to determine the optimal treatment for unresectable stage III EGFRm NSCLC is warranted.