Real-world experience of consolidation durvalumab after concurrent chemoradiotherapy in stage III NSCLC

Durvalumab consolidation is associated with improved progression-free survival (PFS) and overall survival (OS) following concurrent chemoradiotherapy (CCRT) in unresectable stage III non-small cell lung cancer (NSCLC). Given the heterogeneity of stage III NSCLC patients, it is crucial to evaluate the efficacy and safety of durvalumab consolidation when used in the real-world setting.

Durvalumab consolidation is associated with improved progression-free survival (PFS) and overall survival (OS) following concurrent chemoradiotherapy (CCRT) in unresectable stage III non-small cell lung cancer (NSCLC). However, the benefit of consolidation durvalumab remains uncertain in EGFR patients from the PACIFIC trial. In a real-world durvalumab experience, shared by Dr. Huang, an analysis was set out to determine the efficacy and safety of durvalumab consolidation in unresectable stage III NSCLC in Singapore.

Methods

Between January 2013 and Augustus 2020, outcomes of two cohorts of unresectable stage III NSCLC patients treated at the National University Cancer Institute Singapore were described. One cohort received definitive CCRT alone, another cohort had durvalumab consolidation following CCRT. Primary endpoints were PFS and OS, secondary endpoints were locoregional relapse rate, distant relapse rate and safety. In the durvalumab cohort, the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were collected at baseline and at six weeks and correlated with PFS, OS and risk of pneumonitis.

Real-world durvalumab experience

In total, 95 patients were enrolled in the analysis; 56 received CCRT alone and 39 received durvalumab consolidation following CCRT. The median age was 65 years, 77.9% was male, 72.6% Chinese, 95.8% ECOG PS 0-1, 44.2% stage IIIA disease, 52.6% adenocarcinoma histology, 32.6% harboured EGFR mutations, and PD-L1 tumour proportion score (TPS) was ≥1% in 20.0% of patients. Median PFS was 8.9 months for patients receiving CCRT alone and 22.7 months for patients receiving durvalumab consolidation following CCRT (HR[95%CI]: 0.64[0.34-1.21], p= 0.173). Both EGFR mutation positive and EGFR wild-type (WT) patients benefitted from durvalumab consolidation compared to CCRT alone, with improved PFS at 17.5 vs. 10.9 months and 11.8 vs. 4.5 months, respectively. In addition, median OS was significantly longer in the durvalumab arm as compared to the CCRT alone arm (not reached vs. 21.6 months, HR[95%CI]: 0.32[0.13-0.78], p= 0.012).

In the durvalumab cohort, 74.4% of patients had a partial response after CCRT, and none had progressive disease. However, in the CCRT-alone cohort, the response rate was lower at 43.7% following CCRT, and 21.8% of patients progressed while on CCRT. The locoregional relapse rate and distant relapse rate were 19.6% vs. 5.1% (p= 0.004) and 37.5% vs. 20.5% (p= 0.004) in the CCRT-alone cohort and durvalumab cohort respectively. Furthermore, in the durvalumab cohort, 59% of patients experienced immune-related adverse events (IrAEs) of any grade. Dermatitis (33.3%) and pneumonitis (30.8%) were the most common IrAEs. Grade 2+ pneumonitis was detected in 25% of patients. Most pneumonitis occurred at 3.5 weeks after durvalumab initiation.

Finally, results indicate that baseline NLR may help to predict benefit with durvalumab.

Conclusion

In this real-world experience, durvalumab consolidation post CCRT was associated with a statistically significant improvement in OS and a numerically longer PFS. Larger sample size and longer follow-up are needed to confirm these findings.  Both EGFR-positive and -wild type patients had longer PFS with durvalumab consolidation. Pneumonitis, a common and debilitating complication, occurred early following durvalumab initiation and active surveillance and appropriate management for pneumonitis are therefore necessary while receiving durvalumab consolidation.

Reference

Huang Y, et al. Real-World Experience (RWE) of Consolidation Durvalumab After Concurrent Chemoradiotherapy (CCRT) In Stage III NSCLC. Presented at the 2021 World Conference on Lung Cancer; Abstract P28.01.