In a study reported in JAMA Network Open, Charu Aggarwal, MD, MPH, and colleagues found that patients with advanced solid cancers and a high tumor mutational burden (TMB-H) had improved overall survival with immune checkpoint inhibitor therapy vs those with a low tumor mutational burden (TMB-L).
Charu Aggarwal, MD, MPH
Study Details
The study involved data from patients in the Tempus database (covering 199 community sites and 101 academic sites) who underwent next-generation sequencing (Tempus xT) between 2018 and 2022. Patients with advanced solid tumors across eight cancer types who were treated with U.S. Food and Drug Administration–approved immune checkpoint inhibitors in the first- or second-line setting were included in the analysis. The primary outcome measure was association of TMB-H (≥ 10 mut/mb) vs TMB-L with overall survival.
Key Findings
The total evaluable cohort consisted of 674 patients. Mean age was 69.4 years, 40.2% were female, and 64.5% were White. The most common cancers in the cohort were non–small cell lung cancer (NSCLC, 49.0%), bladder cancer (22.0%), and head and neck squamous cell carcinoma (14.8%). A total of 206 patients (30.6%) had TMB-H cancers.
In the total evaluable cohort, median follow-up was 7.2 months (interquartile range [IQR] = 3.2–14.1 months). Median overall survival was significantly better in the TMB-H group vs the TMB-L group (17.4 vs 12.7 months; hazard ratio [HR] = 0.72, upper 95% confidence interval bound [UCB] = 0.91, P = .01).
In a prospective subset of 403 patients treated with immune checkpoint inhibitors after TMB testing, median follow-up was 9.4 months (IQR = 5.1–15.4 months). Patients with TMB-H cancers (n = 135, 33.5%) vs TMB-L cancers had significantly better overall survival (median = 32.8 months vs 14.9 months; HR = 0.61; UCB = 0.84, P = .005), progression-free survival (HR = 0.62, UCB = 0.82, P = .003), and time to disease progression (HR = 0.67, UCB = 0.92, P = .02).
In the prospective subset, overall survival benefit in patients with TMB-H cancers was observed irrespective of immune checkpoint inhibitor used, including pembrolizumab (n = 339; HR = 0.67, UCB = 0.94, P = .03) and other immune checkpoint inhibitors (n = 64; HR = 0.37, UCB = 0.85, P = .03), and in analysis adjusting for PD-L1 expression and microsatellite stability status (n = 403; HR = 0.67, UCB = 0.92, P = .02).
In the prospective subset, 1-year overall survival rates were numerically higher (not powered for statistical testing) in TMB-H vs TMB-L patients with NSCLC (n = 242), bladder cancer (n = 77), colorectal cancer (n = 23), melanoma (n = 14), and other cancers (n = 4), but not in those with head and neck squamous cell carcinoma (n = 43).
The investigators concluded, “In this cohort study of patients with advanced solid tumors treated with immune checkpoint inhibitors in diverse clinics, TMB-H cancers were significantly associated with improved clinical outcomes compared with TMB-L cancers.”
Jyoti D. Patel, MD, of the Division of Hematology/Oncology, Northwestern University, is the corresponding author for the JAMA Network Open article.
Disclosure: The study was supported by Tempus Labs. For full disclosures of the study authors, visit jamanetwork.com.
