Assessment of NETest Clinical Utility in a U.S. Registry-Based Study

Abstract

Background: The clinical relevance of molecular biomarkers in oncology management has been recognized in breast and lung cancers. We evaluated a blood-based multigene assay for management of neuroendocrine tumors (NETs) in a real-world study (U.S. registry NCT02270567). Diagnostic accuracy and relationship to clinical disease status in two cohorts (treated and watch-and-wait) were evaluated.

Materials and methods: Patients with NETs (n = 100) were followed for 6-12 months. Patients' primary tumors were gastroenteropancreatic (68%), lung 20%, and of unknown origin (12%). Characteristics included well-differentiated, low-grade tumors (97%), stage IV disease (96%); treatment with surgery (70%); and drug treatment (56%). NETest was measured at each visit and disease status determined by RECIST. Scores categorized as low (NETest 14%-40%) or high (≥80%) defined disease as stable or progressive. Multivariate analyses determined the strength of the association with progression-free survival (PFS).

Results: NETest diagnostic accuracy was 96% and concordant (95%) with image-demonstrable disease. Scores were reproducible (97%) and concordant with clinical status (98%). The NETest was the only feature linked to PFS (odds ratio, 6.1; p < .0001). High NETest correlated with progressive disease (81%; median PFS, 6 months), and low NETest correlated with stable disease (87%; median PFS, not reached). In the watch-and-wait cohort, low NETest was concordant with stable disease in 100% of patients, and high NETest was associated with management changes in 83% of patients. In the treated cohort, all low NETest patients (100%) remained stable. A high NETest was linked to intervention and treatment stabilization (100%). Use of NETest was associated with reduced imaging (biannual to annual) in 36%-38% of patients.

Conclusion: Blood NETest is an accurate diagnostic and can be of use in monitoring disease status and facilitating management change in both watch-and-wait and treatment cohorts.

Implications for practice: A circulating multigene molecular biomarker to guide neuroendocrine tumor (NET) management has been developed because current biomarkers have limited clinical utility. NETest is diagnostic (96%) and in real time defines the disease status (>95%) as stable or progressive. It is >90% effective in guiding treatment decisions in conjunction with diagnostic imaging. Monitoring was effective in watch-and-wait or treatment groups. Low levels supported no management change and reduced the need for imaging. High levels indicated the need for management intervention. Real-time liquid biopsy assessment of NETs has clinical utility and can contribute additional value to patient management strategies and outcomes.

Keywords: Biomarker; Carcinoid; Liquid biopsy; NET transcripts; Neuroendocrine; Registry.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

© AlphaMed Press 2018.

Figures

Figure 1.

Diagnostic efficacy and concordance with imaging. (A): The NETest was concordant with image‐confirmed disease in 96% of patients. (B): CgA was ordered for 53 of the 100 patients. The NETest was positive in all 53 (100%). CgA was positive in 25%. NETest positivity was significantly greater than CgA (p = .0004). Abbreviation: CgA, chromogranin A.

Figure 2.

Concordance between NETest and clinical disease status. Stable disease was associated with a low NETest (≤40%) in 87% of patients (54/62); progressive disease was associated with a high score (≥80%) in 81% of patients (21/26).

Figure 3.

Relationship between NETest score and clinical management. (A): In the watch‐and‐wait cohort, a low score was associated with no treatment intervention in 93% of patients. A high score led to a treatment intervention in 71%. (B): In the treatment cohort, a low score was associated with no change in treatment in 100% of patients. A high score led to a treatment modification in 86%. Abbreviations: PD, progressive disease; SD, stable disease.

Figure 4.

Relationship between NETest score and PFS. (A): In the entire cohort (n = 100), NETest scores significantly differentiated mPFS. For patients with a low score, mPFS was not reached; an intermediate score was associated with an mPFS of 6 months, and a high score was associated with an mPFS of 3 months. This was highly significant (χ2, 59.9; p < .0001). The HR was 0 for a low score, 3.5 for an intermediate score, and 6.4 for a high score. (B): In the watch‐and‐wait cohort, a low score was associated with mPFS of 12 months. A high score was associated with a mPFS of 3 months. This difference was significant (HR, 29.9; p < .0001). (C): In the treatment cohort, a low score was associated with an mPFS not reached. A high score was associated with an mPFS of 3 months. This difference was significant (HR, 31.5; p < .0001). Abbreviations: CI, confidence interval; HR, hazard ratio; mPFS, median PFS; PFS, progression‐free survival.

Figure 5.

Impact on imaging of a low NETest score. (A): In the watch‐and‐wait cohort, 10 patients (38%) switched from biannual to annual imaging with an overall decrease in imaging events of 19%. (B): In the treatment cohort, a low score resulted in 13 patients (36%) changing from biannual to annual imaging, for an overall reduction of 18%.