Dr. Zhu on TMB in Lung Cancer

Viola W. Zhu, MD, PhD, medical oncologist/hematologist, University of California, Irvine, discusses tumor mutational burden (TMB) in lung cancer.

TMB is an emerging biomarker that may predict response to immunotherapy, says Zhu. However, there is no consensus in terms of how to define a TMB-high population. National Comprehensive Cancer Network (NCCN) guidelines list the CheckMate-227 and CheckMate-026 trials for reference for patients with TMB-high lung cancer, says Zhu.

In the CheckMate-227 trial, the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) and was compared with nivolumab plus chemotherapy or chemotherapy alone. The progression-free survival (PFS) in the TMB-high subgroup, defined as 10 mutations/megabase or higher, indicated an improvement in PFS. However, the overall survival data were not deemed to be statistically significant, says Zhu.

The NCCN, however, do list this regimen as a potential option for patients with non—small cell lung cancer. The KEYNOTE-026 trial was a negative study that compared nivolumab with chemotherapy in patients with PD-L1 expression ≥5%. According to a subgroup analysis, patients with TMB-high tumors experienced an improvement in PFS. As such, nivolumab is listed as a possible treatment option for patients with TMB-high lung cancer in the NCCN guidelines.