Concurrent chemoradiotherapie met durvalumab verlengt overleving bij stage III longkanker in de praktijk

BACKGROUND: The introduction of consolidation durvalumab after chemoradiotherapy (CRT) for unresectable stage 3 non-small cell lung cancer (NSCLC), as established by the PACIFIC trial, has transformed survival outcomes. However, its impact remains uncertain in populations characterised by high levels of socioeconomic deprivation, multimorbidity, and historically poorer cancer outcomes compared to other regions. MATERIALS/METHODS: This retrospective observational cohort study included all patients with stage III unresectable NSCLC who received radical (chemo)radiotherapy, between 01/01/2017 - 31/12/2022. Clinical outcomes were compared across treatment groups: radiotherapy alone, sequential CRT, concurrent CRT, and concurrent CRT followed by consolidation durvalumab. Multivariate Cox proportional hazards regression was employed to identify factors associated with outcomes. RESULTS: 656 patients with stage III NSCLC treated with radical radiotherapy were included. The median age was 69 years, and 54% were male. Most patients had a PS of 0 or 1 (81%), the median Charlson Comorbidity Index (CCI) was 3 (2 - 5) and 62% resided in the most deprived socioeconomic quintiles. Radiotherapy alone was the most common treatment (59%). Administration of radiotherapy alone appeared to be influenced by older age and higher performance status, and not by deprivation or objective functional measurements of multimorbidity (i.e. CCI). Reflex biomarker testing improved over time, while the use of sequential CRT declined, and the rates of concurrent CRT, with or without durvalumab, increased.Multivariate regression demonstrated that patients receiving concurrent CRT plus durvalumab achieved superior 2 year progression-free survival (PFS) compared with concurrent CRT alone (HR 0.51, 0.33 - 0.78, p=0.002). Patients treated with radiotherapy alone had the poorest 2-year OS and PFS, independent of other confounders. Delivering a full year of durvalumab was challenging, with 55% of patients who started durvalumab being unable to complete treatment. However, 53% of those who discontinued durvalumab early remained disease-free at 2 years. CONCLUSION: This study reinforces the progression-free survival benefit of consolidation durvalumab in patients able to undergo concurrent CRT within a large real-world cohort. Although the cohort was socially deprived and comorbid, the high proportion of patients receiving radical radiotherapy alone, and their associated poorer survival outcomes, were not explained by this, revealing a mismatch between objective fitness and clinical decision making, The associated poorer survival outcomes from radiotherapy alone highlights the urgent need to optimise treatment strategies for such patients.