We used a real-world database (GuardantINFORM^TM) to analyze the treatment choices for patients with mCRC who underwent next-generation sequencing of circulating tumor DNA (ctDNA) using a commercially available test (Guardant360^®) after first- or second-line therapy. From 18,875 patients with claims for CRC, 1064 had confirmed metastatic disease and sufficient histories for analysis (median age 59 years, 44.8% female, 44.5% left-sided). ctDNA was detectable for 997/1064 (93.7%) patients. Clinically actionable molecular profiles were present for 507/1064 (47.7%) patients, including those who had not received targeted therapy in the previous line (410/926, 44.3%). Second- or third-line targeted therapies were administered to 338/1064 patients (31.8%) and were considered matched for 193/338 (57.1%) patients. Therapies administered after testing were informed by the ctDNA results in 56.7% of patients overall (603/1064). Time to treatment discontinuation was most favorable for patients with a clinically actionable ctDNA profile who received matched therapy. This analysis demonstrates the real-world clinical value of plasma-based comprehensive genomic profiling for selecting appropriate molecular-targeted therapies in mCRC patients with disease progression after first- or second-line therapy.

Circulating tumor DNA (ctDNA) holds promise as a biomarker for predicting clinical responses to therapy in solid tumors, and multiple ctDNA assays are in development. However, the heterogeneity in ctDNA levels prior to treatment (baseline) across different cancer types and stages and across ctDNA assays has not been widely studied. Friends of Cancer Research formed a collaboration across multiple commercial ctDNA assay developers to assess baseline ctDNA levels across five cancer types in early- and late-stage disease. This retrospective study included eight commercial ctDNA assay developers providing summary-level de-identified data for patients with non-small cell lung cancer (NSCLC), bladder, breast, prostate, and head and neck squamous cell carcinoma following a common analysis protocol. Baseline ctDNA levels across late-stage cancer types were similarly detected, highlighting the potential use of ctDNA as a biomarker in these cancer types. Variability was observed in ctDNA levels across assays in early-stage NSCLC, indicative of the contribution of assay analytical performance and methodology on variability. We identified key data elements, including assay characteristics and clinicopathological metadata, that need to be standardized for future meta-analyses across multiple assays. This work facilitates evidence generation opportunities to support the use of ctDNA as a biomarker for clinical response.

To evaluate biomarker-targeted therapy utilization, healthcare costs, and overall survival (OS) with comprehensive genomic profiling (CGP), small panel, or no molecular testing for patients with metastatic non-small cell lung cancer (mNSCLC). This retrospective claims analysis identified patients with newly diagnosed mNSCLC (index date) from 08/01/2020-12/31/2022, using the Optum Labs Data Warehouse. Patients were grouped by first molecular testing approach: 1) CGP (>50 genes); 2) small panel (individual gene or ≤50 gene panel); or 3) no molecular testing. Post-diagnosis outcomes assessed during variable follow-up included biomarker-targeted therapy use, healthcare costs per patient per month (PPPM) during the first 180 days, and OS. Among 8783 patients identified, the molecular testing approach consisted of 41.4% CGP, 30.3% small panel, 23.4% no testing, and 4.9% unassigned. For CGP, the specimen type was 40.6% blood, 37.2% tissue, 2.8% blood and tissue, and 19.4% undefined. Use of biomarker-targeted therapy was higher with CGP than small panel testing (12.4%vs. 7.7%, P < 0.001). In an exploratory analysis, biomarker-targeted therapy use was higher with blood vs. tissue CGP (14.3%vs. 11.2%, P = 0.01). Among treated patients, adjusted OS did not differ significantly for CGP and small panel testing (HR 1.03, 95% CL 0.94 to 1.12, P = 0.58). Among treated patients, mean total healthcare costs PPPM were similar between CGP and small panel testing across both Medicare Advantage ($17,974 vs. $17,593, P = 0.31) and commercial ($40,655 vs. $39,802, P = 0.68) insurance and remained consistent after adjusting for baseline characteristics. In mNSCLC, patients with CGP received biomarker-targeted therapy at higher rates than patients with small panel testing. Among treated patients, adjusted analyses showed no statistically significant difference in OS between CGP and small panel testing, and total healthcare costs were comparable between testing approaches.