肺癌 免疫治療如何精準治療: PD-L1 高低不重要？！癌突變壓力(Tumor mutation burden) 成關鍵？

CheckMate 227 trial in advanced lung cancer by Dr. Borghaei.

Tumor mutation burden matters than PD-L1: 

1, regardless of the level of PD-L1 expression or histology, patients who had this biomarker of a high tumor mutational burden above a certain threshold had a better outcome compared to patients with a relatively low tumor mutational burden, in terms of PFS and response rate, with the combination of ipilimumab plus nivolumab compared to chemotherapy alone.

2, even in this population of PD-L1–negative patients, a high tumor mutational burden was associated with better PFS and better duration of response with ipilimumab plus nivolumab than either chemotherapy alone or nivolumab plus chemotherapy.

3, patients have PD-L1–negative tumors and a low tumor mutational burden, the addition of nivolumab to chemo or ipilimumab to nivolumab didn’t really provide additional benefit over chemotherapy alone.

Side effects: add nivolumab to chemotherapy there are more side effects compared to chemotherapy alone. But interestingly, in this analysis, the group of patients that got ipilimumab plus nivolumab had a lower percentage of the grade 3 and 4 severe side effects. In the chemotherapy-plus-nivolumab group, the grade 3 and 4 toxicities were close to 50%—but only 25% and 35% of patients in the ipilimumab-plus-nivolumab group and chemotherapy-alone group experienced these toxicities.

*Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

* Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. This results in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and and plays a key role in in tumor evasion from host immunity.