Tumor mutational burden may be linked to immunotherapy response in advanced cancers
Click Here to Manage Email Alerts
Key takeaways:
- Cancers with high vs. low tumor mutational burden appeared significantly associated with longer OS and PFS after immunotherapy.
- Researchers noted the OS benefit regardless of immune checkpoint inhibitor used.
Cancers with high vs. low tumor mutational burden appeared significantly associated with improved clinical outcomes among patients treated with immune checkpoint inhibitors, according to data published in JAMA Network Open.
“This study demonstrates the value of clinical genomic data sets for the assessment of evolving molecular biomarkers and clinical outcomes in diverse settings which are more representative of clinical practice patterns than clinical trials,” Charu Aggarwal, MD, MPH, Leslye M. Heisler associate professor for lung cancer excellence at University of Pennsylvania’s Perelman School of Medicine, associate director for Penn Center for Precision Medicine and associate director of Penn Center for Cancer Care Innovation, as well as a Healio | HemOnc Today Associate Medical Editor, and colleagues wrote.
Background and methodology
Few studies have assessed the association between tumor mutational burden (TMB) and clinical outcomes among a large cohort of patients with a variety of advanced cancers. Aggarwal and colleagues used the Tempus database to evaluate patients with advanced solid tumors who underwent next-generation sequencing between 2018 and 2022 and received treatment with immune checkpoint inhibitors (ICIs) in a first-line or second-line setting. The retrospective, observational data originated from 300 practice sites (199 community, 101 academic).
The cohort included 674 patients (median age, 69.4 years; interquartile range, 28.6-89.8; 64.5% white; 59.8% men) with tumors across eight cancer types and over 20 histologies whose tumors had been sequenced with the Tempus xT (Tempus Labs) targeted gene panel assay. The most common advanced cancers included non-small cell lung cancer (49%), bladder cancer (22%), and head and neck squamous cell carcinoma (14.8%). Treatment consisted of FDA-approved PD-1/PD-L1 and/or CTLA-4 ICIs.
Association of TMB binary category (high vs. low) with OS among treated patients served as the primary outcome. Researchers defined TMB-high tumors as those with 10 or more mutations per megabase. Secondary outcomes included PFS and time to progression.
Median follow-up was 7.2 months (IQR range, 3.2-14.1).
Results, next steps
TMB-high cancers (30.6% of patients) appeared significantly associated with longer OS than TMB-low cancers (HR = 0.72; upper confidence bound (UCB) = 0.91).
Among a prospective subset of 403 patients treated with ICIs following TMB testing, patients with TMB-H cancers (33.5%) appeared significantly associated with longer OS (HR = 0.61; UCB = 0.84; P = .005), PFS (HR = 0.62; UCB = 0.82; P = .003) and time to progression (HR = 0.67; UCB = 0.92; P = .02) than patients with TMB-L cancers.
Researchers noted an OS benefit regardless of the type of ICI used, including pembrolizumab (Keytruda, Merck; n = 339; HR = 0.67; UCB = 0.94; P = .03) or other ICIs (n = 64; HR = 0.37; UCB = 0.85; P = .03), and after adjusting for PD-L1 and microsatellite stability status (n = 403; HR = 0.67; UCB = 0.92; P = .02).
The results provide new evidence regarding the importance of the TMB biomarker among a diverse patient cohort.
“The value of TMB in the first-line ICI therapy setting is of particular importance clinically since the FDA TMB-based pembrolizumab approval remains limited to the pretreated patient population,” Aggarwal and colleagues wrote. “Furthermore, as the frontline immunotherapy treatment landscape evolves ... robust biomarkers such as TMB will be important for assessing who may benefit most from these new ICI treatments.”
Collapse
Aggarwal C, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2023.11181.
Click Here to Manage Email Alerts