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

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.

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.

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.

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