Recent advances and future perspectives in adjuvant and neoadjuvant immunotherapies for lung cancer

The superior efficacy of immune checkpoint inhibitors for the treatment of advanced non-small cell lung cancer has inspired many clinical trials to use immune checkpoint inhibitors in earlier stages of lung cancer worldwide. Based on the theoretical feasibility that neoantigens derived from a tumor tissue are present in vivo, some clinical trials have recently evaluated the neoadjuvant, rather than the adjuvant, use of immune checkpoint inhibitors. Some of these trials have already produced evidence on the safety and efficacy of immune checkpoint inhibitors in a neoadjuvant setting, with a favorable major pathologic response and few adverse events. In the most impactful report from Johns Hopkins University and the Memorial Sloan Kettering Cancer Center, the programed death-1 inhibitor nivolumab was administered to 21 patients in a neoadjuvant setting. The authors reported a major pathologic response rate of 45%, with no unexpected delay of surgery related to the adverse effects of nivolumab. The adjuvant as well as the neoadjuvant administration of immune checkpoint inhibitors has also been considered in various clinical trials, with or without the combined use of chemotherapy or radiotherapy. The development of appropriate biomarkers to predict the efficacy of immune checkpoint inhibitors is also underway. The expression of programed death ligand-1 and the tumor mutation burden are promising biomarkers that have been evaluated in many settings. To establish an appropriate method for using immune checkpoint inhibitors in combination with surgery, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group will manage clinical trials using a multimodality treatment, including immune checkpoint inhibitors and surgery.