Concurrent chemoradiotherapy (CCRT) and adjuvant durvalumab are the recommended treatments for people with stage III non-small-cell lung cancer (NSCLC). However, despite the increased chance of survival provided by immunotherapy in this situation, just one-third of patients were alive and disease-free at 5 years. Therefore, to improve patient outcomes in that situation, novel treatment approaches were being developed, including immunotherapy concurrent with CCRT and/or sequential chemoradiotherapy, consolidation immunotherapy after sequential chemoradiotherapy, and various anti-programmed cell death protein 1/programmed death-ligand 1 [anti-PD-(L)1] antibodies.

The timing of immunotherapy treatment and the inclusion and exclusion criteria for patients vary in the scenario, making cross-trial comparability extremely difficult. For a study, researchers sought to describe the outcomes of clinical trials testing immune therapy in unresectable stage III NSCLC and thoroughly examine the scientific underpinnings, challenges, and possible advantages of these treatments. In addition, the probable pathways of synergism between chemotherapy, radiation treatment, and various monoclonal antibodies were highlighted, along with how this influences the tumor immune milieu.

The discussion also included the designs and issues raised by current clinical studies. Finally, they discussed unanswered issues and unfulfilled clinical requirements, such as the requirement for predictive biomarkers (e.g., radiomics and circulating tumor DNA). Finding distinctive patient subgroups to target anticancer treatment was essential, particularly for diverse conditions like stage III NSCLC.