AROUND one-third of patients with non-small-cell lung cancer (NSCLC) are diagnosed with stage III, locally advanced disease. Historically, the standard treatment for unresectable cases was chemoradiation followed by observation. However, since 2018, consolidation therapy with durvalumab, an anti-PD-L1 immunotherapy, has significantly improved survival, extending five-year overall survival from 33.4% to 42.9% according to the PACIFIC trial.
Despite this advance, most patients with unresectable stage III NSCLC still succumb to the disease. New strategies are being explored to further improve outcomes. One such approach is combining PD-1 and CTLA-4 inhibitors, which has shown promise in metastatic NSCLC. Additionally, the optimal duration of consolidation immunotherapy remains unclear. Many patients do not complete the full 12 months due to toxicity, yet outcomes remain similar among those who stop early.
The BTCRC LUN 16-081 trial is the first to evaluate a shorter, six-month course of consolidation immunotherapy using nivolumab alone or in combination with ipilimumab. Both arms improved 18-month progression-free survival (PFS) over historical controls, suggesting that shorter durations may still be effective.
However, the combination arm had higher toxicity, including more frequent hospitalisations and higher rates of pneumonitis. Most side effects were manageable and resolved with treatment. Interestingly, the study also found no clear correlation between tumour PD-L1 expression and outcomes, contrasting with earlier trials.
While the trial confirms the value of immunotherapy after chemoradiation, it does not change the current standard of one year of durvalumab. Instead, it raises important questions about duration, timing, and personalisation of treatment. Future trials, such as CheckMate 73L and PACIFIC9, are exploring new combinations and biomarker-driven approaches to refine therapy.
In conclusion, LUN 16-081 supports the continued investigation of shorter immunotherapy regimens and combination strategies. The results, although not practice-changing yet, provide a foundation for future research aiming to improve outcomes while reducing treatment burden and toxicity.
Reference
Durm G et al. Randomized phase II study of consolidation immunotherapy with nivolumab and ipilimumab or nivolumab alone following concurrent chemoradiotherapy for unresectable stage IIIA/IIIB non-small-cell lung cancer (NSCLC): Big Ten Cancer Research Consortium LUN16-081. J Immunother Cancer. 2025;13(7):e010316.
