Real-World Insights into the Impact of Durvalumab on Stage III Unresectable Non-Small Cell Lung Cancer-A Narrative Review.

Objective: Stage III Non-Small Cell Lung Cancer (NSCLC) has a poor prognosis, with median survival ranging from 9 to 34 months. The PACIFIC trial demonstrated that durvalumab after platinum-based chemoradiotherapy (CRT) improves overall survival (OS) and progression-free survival (PFS). This review evaluates real-world evidence (RWE) on durvalumab's efficacy and safety, focusing on patient characteristics, prognostic factors, treatment protocols, and outcomes beyond progression.

Methods: A literature search of PubMed, Embase, and Google Scholar identified 49 observational studies published from January 2017 to August 2024 on unresectable stage III NSCLC. Clinical trials, early-stage disease, and alternative treatments were excluded.

Results: Compared to the PACIFIC trial, real-world patients were older, had poorer ECOG performance (≥2), and more comorbidities like COPD. Despite this, durvalumab provided consistent survival benefits. Positive prognostic factors included non-squamous histology, high PD-L1 expression, and timely durvalumab initiation (≤42 days post-CRT). Most radiotherapy regimens mirrored PACIFIC (54-66 Gy). Concomitant CRT was used in 90% of cases, with sequential CRT for frail patients. Chemotherapy regimens varied. Immune-mediated pneumonitis was a major adverse event, with incidence rates between 15% and 100%. Severe cases led to treatment discontinuation, impacting survival. Treatment beyond progression remains uncertain, with limited benefits from immunotherapy rechallenge.

Conclusions: RWE supports durvalumab's efficacy, emphasizing the need for personalized treatment strategies and further research to improve long-term outcomes.