Durvalumab consolidation therapy in EGFR-mutated NSCLC patients: Real-World insights from the PACIFIC-R study

The phase 3 PACIFIC trial established consolidation durvalumab as the standard of care for unresectable stage III non-small cell lung cancer (NSCLC) patients who had not progressed after platinum-based chemoradiotherapy. The real-world effectiveness of this treatment was confirmed through PACIFIC-R.  This new analysis revealed that patients harbouring EGFR mutations had lower real-world progression-free survival (RwPFS) compared to EGFR-wildtype patients, while overall survival (OS) remained similar between these groups.

The phase 3 PACIFIC trial established consolidation durvalumab for up to twelve months as a global standard of care for patients with unresectable, stage III non-small cell lung cancer (NSCLC) and no progression after platinum-based chemoradiotherapy. The primary analyses from PACIFIC demonstrated improved overall survival (OS, HR: 0.72) and progression-free survival (PFS, HR: 0.55) with durvalumab, and a subsequent 5-year follow-up analysis demonstrated that the benefit with durvalumab was sustained over time. The real-world effectiveness of this regimen was confirmed in PACIFIC-R, a study of patients who received durvalumab through the global PACIFIC early access programme (EAP). However, there remains uncertainty regarding the effectiveness of consolidation immunotherapy in patients with EGFR-mutated NSCLC. This analysis aims to shed light on this matter by presenting outcomes from PACIFIC-R according to EGFR mutation status.

Methods

PACIFIC-R is an international, observational study conducted as a retrospective review of established medical records. Eligible patients were aged ≥18 years, had unresectable, stage III NSCLC regardless of PD-L1 expression and no evidence of progression following platinum-based concurrent or sequential chemotherapy. Additionally, these patients had started durvalumab (10 mg/kg IV; Q2W) within the EAP between September 2017 and December 2018. The data were analysed at different time points, with this analysis corresponding to the 3-year assessment. The primary endpoints were real-world PFS (rwPFS) and OS. RwPFS and OS, according to EGFR status was an exploratory objective.

Results

As of November 2021 (end of the third chart extraction), the full analysis set comprised 1,154 patients recruited across ten countries, including eight European countries plus Australia and Israel. Previous reports from this study indicated 2-year OS and PFS rates of 72.3% and 50.1%, respectively. With extended follow-up, the 3-year OS and PFS rates stand at 63.2% and 42.2%, supporting the continued use of consolidation durvalumab following chemoradiotherapy (the PACIFIC regimen), for patients with unresectable NSCLC. Among the patients, 466 of 1,154 patients had documented EGFR status based on local testing. Of these, 44 (9.4%) had EGFR-mutated NSCLC, while 422 (90.6%) had EGFR-wildtype NSCLC. PD-L1 expression levels ≥1% were observed in 76.3% and 76.9% of EGFR-mutated and wildtype patients, respectively.

Investigator-assessed PFS by EGFR status was 10.6 months for EGFR-mutated patients vs. 26.4 months for EGFR-wildtype patients. At two years, PFS rates were 38.6% vs. 52.5%, while they were 29.0% and 45.0% at three years. However, no differences were observed in OS (46.3 months vs. not reached in the EGFR-mutated and wildtype groups, respectively), with 2-year OS rates of 79.5% vs. 76.7%, and 3-year rates of 64.9% vs. 67.9%. Of note, the outcomes observed in patients with EGFR-mutated NSCLC receiving durvalumab in PACIFIC-R were generally consistent with those in the corresponding subgroup from the PACIFIC trial. However, data from real-world studies and clinical trials should be compared with caution owing to differences in the study design and methods of data collection/analysis. Time to death or distant metastasis (TTDM) was shorter in EGFR-mutant patients (24.7 vs. 38.6 months in wildtype patients), with 2-year TTDM rates of 52.1% vs. 62.9%, and 3-year TTDM rates of 35.3% vs. 52.9%. Time to first subsequent treatment was also shorter among patients with EGFR-mutated vs. wildtype NSCLC (16.7 vs. 43.1 months; 3-year rates were 33.3% vs. 55.4%). Importantly, 20 of 44 (45.5%) patients with EGFR-mutated NSCLC experienced distant metastasis. Regarding adverse events, 56.8% of patients with EGFR-mutated NSCLC experienced adverse events of special interest (AESIs), with pneumonitis being the most common AESI (20.5%), and the most common AESI leading to discontinuation of durvalumab (11.4%).

Conclusions

RwPFS was lower in the EGFR-mutated group compared to the EGFR-wildtype group, while OS was similar between these groups. Outcomes for patients with EGFR-mutated NSCLC in PACIFIC-R were consistent with PFS and OS findings for this subpopulation in the durvalumab arms of the PACIFIC trial.  However, these data should be interpreted with caution due to the small number of patients with identified EGFR mutations and the PACIFIC-R study retrospective nature.

Reference

Peters S. Real-world outcomes with durvalumab after chemoradiotherapy in unresectable stage III EGFR-mutated NSCLC (PACIFIC-R). Presented at WCLC 2023; Abstract OA12.05