Patients with advanced cancer have better outcomes if they have a high tumor mutational burden (TMB) prior to treatment with immune checkpoint inhibitors (ICIs), according to a study published in JAMA Network Open.
Researchers found that patients with high TMB had better overall survival (OS), progression-free survival, and time to progression than patients with low TMB.
The study included 674 patients with advanced solid tumors who underwent sequencing with Tempus xT. The patients had non-small cell lung cancer (49.0%), bladder cancer (22.0%), head and neck cancer (14.2%), melanoma (7.1%), colorectal cancer (5.8%), and other cancers.
Patients were treated at 300 sites. They received 1 of 7 approved ICIs in the first- or second-line setting. The most commonly used ICI was pembrolizumab (83.1%).
Overall, 30.6% of patients had high TMB. The median OS was significantly longer in patients with high TMB than in those with low TMB — 17.3 months and 12.7 months, respectively (hazard ratio [HR], 0.72; P =.01).
The researchers also looked at a prospective subset of 403 patients who were treated with ICIs after TMB testing. Of these patients, 33.5% had high TMB.
In the prospective subset, the median OS was 32.8 months among patients with high TMB and 14.9 months in patients with low TMB (HR, 0.61; P =.005). Patients with high TMB also had significantly longer progression-free survival (HR, 0.62; P =.003) and time to progression (HR, 0.67; P =.02) than patients with low TMB.
In the prospective subset, the high-TMB cohort had improvements in OS regardless of the ICI used. High TMB was associated with improved OS in patients who received pembrolizumab (HR, 0.67; P =.03) and those who received a different ICI (HR, 0.37; P =.03).
“The study findings demonstrate that the TMB category identified from the xT NGS targeted gene panel assay is a robust, reproducible biomarker of clinical benefit to ICIs in a diverse, advanced pancancer cohort treated in multiple clinics,” the researchers concluded.
Disclosures: This research was supported by Tempus Labs. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Aggarwal C, Ben-Shachar R, Gao Y, et al. Assessment of tumor mutational burden and outcomes in patients with diverse advanced cancers treated with immunotherapy. JAMA Netw Open. Published online May 2, 2023. doi:10.1001/jamanetworkopen.2023.11181