Combination Therapy Significantly Improves PFS in Patients With NSCLC With High Tumor Mutational Burden

Patients with locally advanced unresectable non–small cell lung cancer (NSCLC) who had high tumor mutational burden (TMB) had significantly reduced risk of locoregional failure and improved progression-free survival after treatment with definitive chemoradiation and consolidative durvalumab. Researchers published their findings in JAMA Network Open.

“With a median follow-up of more than 2 years following concurrent chemoradiation and consolidative durvalumab, we found that patients with TMB-high tumors had more than a 5-fold reduction in the risk of local-regional failure compared with patients with TMB-low tumors,” wrote corresponding author Narek Shaverdian, MD, and coauthors from Memorial Sloan Kettering Cancer Center in New York, New York.

The cohort study included 81 consecutive patients with unresectable locally advanced NSCLC treated with chemoradiation and adjuvant durvalumab at a multisite tertiary cancer center. Among them, 36 patients had TMB-high tumors (≥10 mutations/megabase).

According to the study, 9% of patients with TMB-high tumors had local-regional failure at 24 months compared with 51% of patients with TMB-low tumors. Rates of progression-free survival at 24 months were 66% among patients with TMB-high tumors and 27% among patients with TMB-low tumors.

Additionally, researchers found KEAP1/NFE2L2-altered tumors were associated with a higher rate of local-regional failure: 52%, compared with 27% among patients with KEAP1/NFE2L2-wildtype tumors.

“These data provide the groundwork to appropriately select patients with unresectable stage III NSCLC for risk-adaptative strategies based on tumor genomics,” the authors advised.

Reference:
Lebow ES, Shepherd A, Eichholz JE, et al. Analysis of tumor mutational burden, progression-free survival, and local-regional control in patents with locally advanced non-small cell lung cancer treated with chemoradiation and durvalumab. JAMA Netw Open. Published online January 5, 2023. doi:10.1001/jamanetworkopen.2022.49591