There are many issues that surround immunotherapy and immunomodulatory drugs, such as PD-L1 inhibitors and associated biomarkers. There is a need to develop universally accepted, standardized criteria for immunohistochemistry-based testing of immune checkpoint markers, in particular for PD-L1. According to the Pulmonary Pathology Society, “most laboratories cannot bear the burden of high‐volume send‐out testing; as a result, it is almost inevitable that predictive diagnostics for immunotherapeutics will become a distributed practice, and inter‐laboratory reproducibility will necessarily become a key element of quality assurance.” Pathologists are being asked to determine the best test to use; however, in the US, the Food and Drug Administration is basing decisions on the test used in the clinical trials and not looking in a universal fashion.
At the same time, there is rapidly evolving interest in genomic biomarkers—in particular tumor mutation burden (TMB)—that may be used in conjunction with or independent of PD-L1 status. It is critical that practicing pathologists make informed decisions about introduction of new biomarkers into their practice. Many new biomarkers have associated high costs both in the form of capital and reagent expenditures or as send out tests. It may be difficult to quickly access unbiased information and pathologists may find themselves unduly influenced by marketing campaigns or by focused and possibly impractical demands from other clinicians.
The primary goal of this guideline is to develop evidence-based recommendations for the testing of immunotherapy/immunomodulatory biomarkers including PD-L1 and TMB in patients with non-small cell lung cancer (NSCLC). Rapid advancement in first and second-line therapy has led to the approval of immune therapies for these patients. Companion diagnostics are required for certain therapies, but there may be variability in methodology, concordance between methods, and standardization.
- In NSCLC patients who are being considered for immuno-oncology neoadjuvant therapy, does PD-L1 and TMB testing improve treatment response rates and survival rates?
- When selecting patients for anti-PD1 and anti-PD-L1 therapy, does testing of different specimen types provide concordant clinical outcomes?
- Does the use of immunotherapy in advanced NSCLC patients with targetable ALK, EGFR, ROS1, or BRAF molecular alterations affect their long-term clinical outcomes?
- When selecting patients for anti-PD1 and anti-PD-L1 therapy, does TMB testing have the analytical validity to identify a complementary population who will benefit from therapy?
- In NSCLC patients with more than one available sample, do multiple samples provide concordant PD-L1 and TMB testing results and downstream clinical outcomes?
- Does clinical validity of PD-L1 testing differ by levels of PD-L1 expression in tumor or immune cells?
- How reproducible are PD-L1 tumor cell scores and immune cell scores across specimen types?
- Do the available PD-L1 assays provide concordant expression profiles when evaluating the same sample and which IHC expression cut-off provides the most reproducible expression categorization across the assays?
Open Comment Period Information
All stakeholders—including pathologists, oncologists, hospital or laboratory managers, and patient advocacy group representatives—are encouraged to review and submit feedback on the draft recommendations by April 30, 2021.
Review the following resources to provide your feedback:
Expert Panel Members
- Lynette M. Sholl, MD, FCAP, Co-chair
- Larissa V. Furtado, MD, FCAP, Co-chair
- Mark Awad, MD, PhD
- Mary Beth Beasley, MD
- Richard Cartun, MS, PhD
- Fernando Lopez-Rios, MD, PhD
- David Hwang, MD, FCAP, PhD
- Gregory P. Kalemkerian, MD
- Mari Mino-Kenudson, MD
- Ajit Paintal, MD
- Lauren Ritterhouse, MD, FCAP
- Paul Swanson, MD, FCAP
- Carol Colasacco, MLIS, SCT(ASCP)
- Kearin Reid, MLIS, MLS(ASCP)
- Lesley Souter, PhD
- Christina B. Ventura, MPH, MT(ASCP)
- Upal Basu Roy, PhD, MPH
- Barbara Ward
- American Society of Clinical Oncology
- Association for Molecular Pathology
- International Association for the Study of Lung Cancer
- Pulmonary Pathology Society
- LUNGevity Foundation
- The information, data, and draft recommendations provided by the College of American Pathologists are presented for informational and public feedback purposes only.
- The draft recommendations and supporting documents will be removed on May 10, 2021.
- The draft recommendations along with the public comments received and completed evidence review will be reassessed by the expert panel in order to formulate the final recommendations. These draft materials should not be stored, adapted, or redistributed in any manner.
- Please note: comments are not posted automatically. All comments will be posted on a weekly basis beginning April 5-May 2, 2021.
- Following the open comment period, the guideline authors will consider all feedback to finalize the recommendations. The final recommendations will be formally published as a guideline in Archives of Pathology & Laboratory Medicine.
- The CAP Pathology and Laboratory Quality Center for Evidence-based Guidelines (Center) develops recommendations related to the practice of pathology and laboratory medicine. Through this work, we and our members continually improve the quality of diagnostic medicine and patient outcomes. For questions, please contact email@example.com.
Review more upcoming CAP evidence-based guidelines by the Center.