Circulating tumor cell assay to non-invasively evaluate PD-L1 and other therapeutic targets in multiple cancers
Raymond Page1, Darshana Patil2, Dadasaheb Akolkar2
1Department of Biochemical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, United States of America.
Abstract:
Biomarker directed selection of targeted anti-neoplastic agents such as immune checkpoint inhibitors, small molecule inhibitors and monoclonal antibodies form an important aspect of cancer treatment. Immunohistochemistry (IHC) analysis of the tumor tissue is the method of choice to evaluate the presence of these biomarkers. However, a significant barrier to biomarker testing on tissue is the availability of an adequate amount of tissue and need for repetitive sampling due to tumor evolution. Also, tumor tissue testing is not immune to inter- and intra-tumor heterogeneity. We describe the analytical and clinical validation of a Circulating Tumor Cell (CTC) assay to accurately assess the presence of PD-L1 22C3 and PD-L1 28.8, ER, PR and HER2, from patients with solid tumors to guide the choice of suitable targeted therapies. Analytically, the test has high sensitivity, specificity, linearity and precision. Based on a blinded case control study, the clinical sensitivity and specificity for PD-L1 (22C3 and 28.8) was determined to be 90% and 100% respectively. The clinical sensitivity and specificity was 83% and 89% for ER; 80% and 94% for PR; 63% and 89% for HER2 (by ICC); and 100% and 92% for HER2 (by FISH), respectively. The performance characteristics of the test support its suitability and adaptability for routine clinical use.
Insights
A new circulating tumor cell (CTC) assay accurately detects cancer biomarkers like PD-L1, ER, PR, and HER2. This blood test offers a less invasive alternative to tissue biopsies for guiding targeted cancer therapy selection.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Biomarkers
Background:
- Biomarker-directed therapies, including immune checkpoint inhibitors and targeted agents, are crucial in cancer treatment.
- Immunohistochemistry (IHC) on tumor tissue is standard for biomarker assessment but faces limitations like insufficient tissue and heterogeneity.
- Tumor evolution necessitates repetitive sampling, posing challenges for traditional tissue-based biomarker testing.
Purpose of the Study:
- To analytically and clinically validate a novel assay using circulating tumor cells (CTCs) for biomarker assessment.
- To evaluate the assay's ability to detect key biomarkers (PD-L1, ER, PR, HER2) in solid tumors.
- To establish CTC assay as a viable method for guiding targeted anti-neoplastic agent selection.
Main Methods:
- Development and validation of a Circulating Tumor Cell (CTC) assay for biomarker detection.
- Analytical validation assessed sensitivity, specificity, linearity, and precision.
- Clinical validation involved a blinded case-control study to determine sensitivity and specificity for various biomarkers.
Main Results:
- The CTC assay demonstrated high analytical performance.
- Clinical validation showed high sensitivity and specificity for PD-L1 (90%, 100%), ER (83%, 89%), PR (80%, 94%), and HER2 (63-100%, 89-92%).
- The assay accurately identified biomarkers from patients with solid tumors, supporting its clinical utility.
Conclusions:
- The validated CTC assay is a sensitive and specific method for detecting multiple cancer biomarkers.
- This blood-based assay overcomes limitations associated with tumor tissue biopsies.
- The CTC assay is suitable for routine clinical use to guide targeted cancer therapy selection.
