COAST to coast.

Maintenance durvalumab after chemoradiation (CRT) for stage III NSCLC improves median survival 18.4 months and 5-year overall survival by 9.8%. But why stop there? COAST was a randomized phase II trial comparing standard CRT plus maintenance durvalumab with or without the addition of either [A] oleclumab (anti-CD73 monoclonal antibody) or [B] monalizumab (anti-NKG2A monoclonal antibody). CD73 is a cell surface enzyme that helps produce extracellular adenosine, which has an immunosuppressive effect in the tumor microenvironment. NKG2A is an inhibitory receptor on natural killer cells  and CD8+ T-cells. Cancer cells overexpress HLA-E, which binds to NKG2A to suppress NK-cell and CD8+ T-cell anti-tumor activity. Oh, it gets better. Radiation can increase tumor expression of CD73, HLA-E, and PD-L1. 189 patients with stage III NSCLC who did not progress after CRT were randomized to one of three arms. Overall response rate was numerically higher with both oleclumab (30%) and monalizumab (35.5%) compared to durvalumab alone (17.9%). Progression free survival at 12 months was also higher with oleclumab (62.6%) and monalizumab (72.7%) than with durvalumab alone (33.9%). | Herbst, J Clin Oncol 2022