Background / Rationale
Although durvalumab following chemoradiotherapy (CRT) is standard of care for unresectable Stage III NSCLC, real world uptake and completion rates remain variable. PACIFIC-R offered observational data from patients already on durvalumab, limiting insight into pre-initiation barriers. This audit aimed to evaluate local durvalumab initiation, completion, toxicity and progression free survival (PFS), with a focus on identifying reasons for non-initiation despite CRT completion.
Methods
A retrospective audit was conducted of 108 patients with histologically confirmed unresectable Stage III NSCLC who completed CRT between 2018-2025. Data was collected on PD L1 status, driver mutations, durvalumab use, toxicity and PFS. Outcomes were compared to PACIFIC-R, where all patients received durvalumab.
Impact on Practice
Of 108 patients who completed CRT, 61.5% commenced durvalumab. Reasons for non-initiation included progression (37.5%), radiation pneumonitis (20%), poor performance status (17.5%), and patient choice due to molecular profiling factors. Among those who started, 35.9% completed twelve months; 25% experienced immune related toxicity, with subsequent discontinuation seen in 17.2%. Median PFS was 16.25 months with durvalumab compared to 8.49 months without.
Compared to PACIFIC-R, this cohort was older (median age 71 vs 64), more co-morbid (median CCI 21) and included a broader range of molecular profiles. While PACIFIC-R reported PDL1 status in a subset, it did not correlate outcomes by PDL1 level. EGFR mutations were the only mutations recorded. In contrast, this audit incorporated molecular data into clinical decision making, with reduced durvalumab uptake in those with low PDL1 status and specific targetable mutations.
Discussion
This audit reveals real world challenges not seen in post-initiation studies. Barriers to durvalumab use include early progression, treatment-related toxicity, comorbidities, and various molecular profiling factors. We pose the need for better patient selection, enhanced toxicity monitoring, and integration of molecular profiling to personalise post-CRT management to improve therapy uptake and durability.