This study will impact clinical practice for the treatment of locally advanced, unresectable non-small cell lung cancer patients. As the authors point out, approximately one-third of patients with non small-cell lung cancer have stage III, locally advanced disease at diagnosis. The treatment of stage III disease is an area in much need of therapeutic breakthroughs, as the outcomes among patients who have received chemoradiotherapy are dismal, with only 15% of patients alive at 5 years. In this phase III study, durvalumab (an anti-programmed death ligand 1 antibody) was compared to placebo for consolidation therapy in patients with stage III disease who had not progressed after 2 or more cycles of platinum-based chemoradiotherapy. Patients received the study drug every 2 weeks for up to 12 months.

The authors found a significant improvement in median progression-free survival at 16.8 months with durvalumab compared to 5.6 months with placebo and a 12-month and 18-month survival for durvalumab compared to placebo of 55.9% vs 35.3% and 44.2% vs 27.0%, respectively. Importantly, the median time to death or distant metastasis was also longer with durvalumab vs placebo (23.2 months vs 14.6 months). The immunotherapy agent was also well tolerated in this study with majority of adverse events being grade 1 or 2, and grade 3 or 4 adverse events occurring in 30% of those receiving durvalumab. Death due to adverse events occurred in 4.4% of patients in the durvalumab group and 5.6% of patients in the placebo group. In the durvalumab group, treatment for immune-mediated adverse events included systemic glucocorticoids in 14.3% of patients, high-dose glucocorticoids in 8.2% of patients, endocrine therapy in 10.7% of patients, and other immunosuppressive agents in 0.4% of patients. 15% of patients in the durvalumab group discontinued the study because of adverse events. Also of note, the investigators looked at PD-L1 expression of tumor cells and the progression-free survival benefit was found irrespective of PD-L1 expression.

Due to this study, durvalumab after definitive chemoradiation therapy for unresectable stage III non small-cell lung cancers has already been added to the NCCN guidelines. Immunotherapy after concurrent chemotherapy and radiation is an appropriate next step to consider in stage III lung cancer patients who meet the criteria of this study due to the significant outcomes demonstrated. —Bobby Daly, MD, MBA