Real-World Safety and Efficacy of Consolidation Durvalumab After Chemoradiation Therapy for Stage III Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis

Abstract

Purpose: Consolidation durvalumab after chemoradiation therapy (CRT) has improved patient outcomes in stage III non-small cell lung cancer (NSCLC) since the practice-changing results of the PACIFIC trial, whereas real-world evidence regarding the PACIFIC regimen has not been systematically reviewed. This meta-analysis comprehensively investigated the real-world toxicity and efficacy of this regimen and identified differences between the real world and clinical trials.

Methods and materials: Real-world studies (RWSs) on patients with stage III NSCLC treated with durvalumab after CRT were identified in MEDLINE, EMBASE, PubMed, and Cochrane Library databases. We summarized the differences in demographic and therapeutic characteristics between RWSs and the PACIFIC trial. A meta-analysis of short-term efficacy and adverse event rates was performed. Subgroup analyses were conducted to identify potential influencing factors.

Results: Thirteen studies involving 1885 patients were included. More elderly and poor-performance-status patients, prolonged interval from CRT completion to durvalumab exceeding 42 days, median infusions of durvalumab <20 cycles, and sequential CRT were observed in the real world. The pooled 12-month overall survival (OS) and progression-free survival (PFS) rates were 90% (95% confidence interval [CI], 83%-98%) and 62% (95% CI, 56%-68%), respectively. Subgroup analysis determined that delay in durvalumab initiation beyond 42 days did not affect 12-month OS (P = .068) or PFS (P = .989). Pooled incidences of all-grade and grade ≥3 pneumonitis were 35% (95% CI, 22%-48%) and 6% (95% CI, 3%-8%), respectively. Higher all-grade pneumonitis rates were observed in the studies of patients with a median age of >65 years (P = .008) and from Asian regions (P = .017), whereas expanded access program-related studies reported significantly lower rates (P = .024).

Conclusions: The safety and short-term efficacy of consolidation durvalumab in real-life use aligns with the PACIFIC trial. RWSs can be helpful for understanding the true efficacy and toxicity of consolidation durvalumab given the less-restrictive eligibility criteria.