Real-World Outcomes of Chemoradiation and Consolidative Durvalumab in Unresectable Stage III Non-Small-Cell Lung Cancer — A Systematic Review

Purpose/Objective(s) The PACIFIC study was a randomized control trial that demonstrated an overall survival (OS) and progression-free survival (PFS) advantage with the use of consolidative Durvalumab following chemoradiation (CRT) in patients with unresectable stage III non-small cell lung cancer (NSCLC). However, its benefit in real-world practice is only emerging. We conducted a systematic review of the literature to determine the real-world evidence to date with respect to outcomes and side effects of consolidative durvalumab following CRT. Materials/Methods A systematic review was conducted using PRISMA guidelines. We searched Embase and Ovid MEDLINE databases for studies in English that included the keywords “durvalumab”, “NSCLC”, and “stage III” from inception to December 2020. The resultant search was screened and abstracted for primary studies that disclosed OS, PFS and/or local control, and adverse events with consolidative durvalumab following CRT. These real-world studies (both published and in abstract form) were reviewed and compared with the outcomes of the PACIFIC clinical trial. Results A total of 691 studies were identified from the initial database search. Applying inclusion and exclusion criteria, 9 real-world studies reported outcomes of applying consolidative durvalumab after CRT. All studies were published between 2018 and 2020. The median number of patients was 29 (range 16-147). The median follow-up was 7-17 months. Reported one-year OS and PFS ranged from 77-94% and 56-65% respectively, compared to 83% and 56% in the PACIFIC study. Median OS was not reached in all real-world studies, and few studies reached median PFS (22%). Local-regional control (∼86% at one year) and time to metastasis or death (67-70% at one year) were inconsistently reported. Adverse events, especially pneumonitis (12-25%), led to discontinuation of durvalumab in 19-36% of patients across the studies, compared to 15% reported in the PACIFIC trial. Conclusion Real-world studies on the use of consolidative durvalumab in stage III NSCLC appear to confirm the OS and PFS advantages reported by the PACIFIC study. Toxicity, including pneumonitis appeared slightly higher than in the PACIFIC trial; the implication of current radiation dose-volume lung parameters in context of consolidative durvalumab will be important for future risk mitigation. Median follow-up was short on average, and updated results with longer follow-up will be important to confirm the clinical efficacy of durvalumab and its safe use in clinical practice.