Patients with non-small cell lung cancer (NSCLC) have better outcomes with chemoradiation plus durvalumab if they have a high tumor mutational burden (TMB), according to a study published in JAMA Network Open

Patients with a high TMB had a higher rate of progression-free survival (PFS) and a lower rate of locoregional failure (LRF) than patients with a low TMB, researchers found.

The researchers looked at 81 consecutive patients with unresectable, locally advanced NSCLC. The patients’ median age was 67 years, 57% were men, 69% had adenocarcinoma, and 71% stage IIIB or IIIC disease. PD-L1 expression levels were below 1% for 31% of patients, and 44% of patients had high TMB (≥10 mutations per megabase).

Continue Reading

Patients received a median of 60 Gy of radiation in 2 Gy daily fractions with concurrent platinum-based chemotherapy. They received durvalumab for a median of 6 months, starting a median of 1.4 months after the completion of chemoradiation.  

The median follow-up was 26 months. The median overall survival (OS) was not reached, and the 24-month OS rate was 72%. The median PFS was 16 months, and the 24-month PFS rate was 45%. The 24-month LRF rate was 31%. 

The 24-month LRF rate was significantly lower in patients with a high TMB than in those with a low TMB — 9% and 51%, respectively (P =.001). 

The 24-month PFS rate was significantly higher in patients with a high TMB than in those with a low TMB — 66% and 27%, respectively (P =.003). 

The researchers also found that patients with KEAP/NFE2L2-altered tumors had an increased risk of LRF. The 24-month LRF rate was 52% in patients with KEAP1/NFE2L2-altered tumors and 27% in patients with wild-type KEAP1/NFE2L2 (P =.05). 

“[W]e did not find KEAP1/NFE2L2 alterations to be associated with poor PFS, suggesting that while these alterations can be associated with radiotherapy outcomes, they may not be as consequential to ICI [immune checkpoint inhibitor] outcomes,” the researchers wrote.

The researchers also found that patients with TMB-high status and wild-type KEAP/NFE2L2 had a very low risk for LRF. The 24-month LRF rate in this group was 7%. 

“These data require validation but suggest that TMB can be used as an integral biomarker to selectively risk-adapt thoracic radiotherapy with both intensification and deintensification strategies,” the researchers concluded. 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


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