Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

Purpose: As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies.

A Blood-based Assay for Assessment of Tumor Mutational Burden in First-line Metastatic NSCLC Treatment: Results from the MYSTIC Study.

Purpose: Tumor mutational burden (TMB) has been shown to be predictive of survival benefit in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors. Measuring TMB in the blood (bTMB) using circulating cell-free tumor DNA (ctDNA) offers practical advantages compared with TMB measurement in tissue (tTMB); however, there is a need for validated assays and identification of optimal cutoffs. We describe the analytic validation of a new bTMB algorithm and its clinical utility using data from the phase III MYSTIC trial.

Establishing guidelines to harmonize tumor mutational burden (TMB): in silico assessment of variation in TMB quantification across diagnostic platforms: phase I of the Friends of Cancer Research TMB Harmonization Project.

Background: Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase of interrogated genomic sequence, demonstrates predictive biomarker potential for the identification of patients with cancer most likely to respond to immune checkpoint inhibitors. TMB is optimally calculated by whole exome sequencing (WES), but next-generation sequencing targeted panels provide TMB estimates in a time-effective and cost-effective manner. However, differences in panel size and gene coverage, in addition to the underlying bioinformatics pipelines, are known drivers of variability in TMB estimates across laboratories.

Baseline Plasma Tumor Mutation Burden Predicts Response to Pembrolizumab-based Therapy in Patients with Metastatic Non-Small Cell Lung Cancer.

Purpose: The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard-of-care therapy for metastatic non-small cell lung cancer (mNSCLC) has not been explored.

Experimental Design: A 500-gene next-generation sequencing panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.

A dataset quantifying polypharmacy in the United States.

Polypharmacy is increasingly common in the United States, and contributes to the substantial burden of drug-related morbidity. Yet real-world polypharmacy patterns remain poorly characterized. We have counted the incidence of multi-drug combinations observed in four billion patient-months of outpatient prescription drug claims from 2007-2014 in the Truven Health MarketScan® Databases.