Challenges to Innovation Arising from Current Companion Diagnostic Regulations and Suggestions for Improvements

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2024 Dec 26

PMID 39724199

Authors

Kelly S Oliner

Michelle Shiller

Peter Schmid

Marianne J Ratcliffe

Aaron J Schetter

Ming-Sound Tsao

Affiliations

Soon will be listed here.

Abstract

A companion diagnostic is a diagnostic test that provides information essential for the safe and effective use of a corresponding therapeutic product. To obtain marketing approval, the companion diagnostic must demonstrate acceptable analytical and clinical performance. Companion diagnostic regulations are intended to protect patients by ensuring quality and consistency of treatment-guiding biomarker testing in clinical trials and clinical practice. However, current regulations have had unintended negative consequences relating to innovation, implementation, and accessibility of precision medicine; increasing complexity and cost burden; and inhibiting development of novel diagnostics and biomarker-targeted therapeutics. We propose a range of practical solutions to these challenges, advocating that regulators, pharmaceutical companies, molecular pathologist groups, and diagnostic companies work together to increase flexibility and promote diagnostic innovation, while maintaining high-quality diagnostic testing to ensure all patients get the most appropriate treatments.

References

Jorgensen J . Missing Companion Diagnostic for US Food and Drug Administration-Approved Hematological and Oncological Drugs. JCO Precis Oncol. 2022; 6:e2200100. DOI: 10.1200/PO.22.00100. View

Lawson N, Scorer P, Williams G, Vandenberghe M, Ratcliffe M, Barker C . Impact of Decalcification, Cold Ischemia, and Deglycosylation on Performance of Programmed Cell Death Ligand-1 Antibodies With Different Binding Epitopes: Comparison of 7 Clones. Mod Pathol. 2023; 36(9):100220. DOI: 10.1016/j.modpat.2023.100220. View

Cooper L, Chen J . Changes in Companion Diagnostic Labelling: Implementation of FDA's April 2020 Guidance for Industry for In Vitro CDx Labeling for Specific Oncology Therapeutic Groups. Ther Innov Regul Sci. 2022; 56(5):689-697. PMC: 9356945. DOI: 10.1007/s43441-022-00422-z. View

Torlakovic E, Lim H, Adam J, Barnes P, Bigras G, Chan A . "Interchangeability" of PD-L1 immunohistochemistry assays: a meta-analysis of diagnostic accuracy. Mod Pathol. 2019; 33(1):4-17. PMC: 6927905. DOI: 10.1038/s41379-019-0327-4. View

Rugo H, Loi S, Adams S, Schmid P, Schneeweiss A, Barrios C . PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer. J Natl Cancer Inst. 2021; 113(12):1733-1743. PMC: 8634452. DOI: 10.1093/jnci/djab108. View

Beaver J, Pazdur R . The Wild West of Checkpoint Inhibitor Development. N Engl J Med. 2021; 386(14):1297-1301. DOI: 10.1056/NEJMp2116863. View

Noske A, Wagner D, Schwamborn K, Foersch S, Steiger K, Kiechle M . Interassay and interobserver comparability study of four programmed death-ligand 1 (PD-L1) immunohistochemistry assays in triple-negative breast cancer. Breast. 2021; 60:238-244. PMC: 8602040. DOI: 10.1016/j.breast.2021.11.003. View

Zehir A, Nardi V, Konnick E, Lockwood C, Long T, Sidiropoulos N . SPOT/Dx Pilot Reanalysis and College of American Pathologists Proficiency Testing for KRAS and NRAS Demonstrate Excellent Laboratory Performance. Arch Pathol Lab Med. 2023; 148(2):139-148. DOI: 10.5858/arpa.2023-0322-CP. View

Valla V, Alzabin S, Koukoura A, Lewis A, Nielsen A, Vassiliadis E . Companion Diagnostics: State of the Art and New Regulations. Biomark Insights. 2021; 16:11772719211047763. PMC: 8512279. DOI: 10.1177/11772719211047763. View

10.

Zajac M, Scott M, Ratcliffe M, Scorer P, Barker C, Al-Masri H . Concordance among four commercially available, validated programmed cell death ligand-1 assays in urothelial carcinoma. Diagn Pathol. 2019; 14(1):99. PMC: 6720992. DOI: 10.1186/s13000-019-0873-6. View

11.

Fitzgibbons P, Bradley L, Fatheree L, Alsabeh R, Fulton R, Goldsmith J . Principles of analytic validation of immunohistochemical assays: Guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2014; 138(11):1432-43. DOI: 10.5858/arpa.2013-0610-CP. View

12.

Tsao M, Kerr K, Kockx M, Beasley M, Borczuk A, Botling J . PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project. J Thorac Oncol. 2018; 13(9):1302-1311. PMC: 8386299. DOI: 10.1016/j.jtho.2018.05.013. View

13.

Salgado R, Bellizzi A, Rimm D, Bartlett J, Nielsen T, Holger M . How current assay approval policies are leading to unintended imprecision medicine. Lancet Oncol. 2020; 21(11):1399-1401. DOI: 10.1016/S1470-2045(20)30592-1. View

14.

Perez-Villatoro F, Oikkonen J, Casado J, Chernenko A, Gulhan D, Tumiati M . Optimized detection of homologous recombination deficiency improves the prediction of clinical outcomes in cancer. NPJ Precis Oncol. 2022; 6(1):96. PMC: 9800569. DOI: 10.1038/s41698-022-00339-8. View

15.

Kim A, Bartley A, Bridge J, Kamel-Reid S, Lazar A, Lindeman N . Comparison of Laboratory-Developed Tests and FDA-Approved Assays for BRAF, EGFR, and KRAS Testing. JAMA Oncol. 2017; 4(6):838-841. PMC: 6145687. DOI: 10.1001/jamaoncol.2017.4021. View

16.

Ratcliffe M, Sharpe A, Midha A, Barker C, Scott M, Scorer P . Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non-Small Cell Lung Cancer. Clin Cancer Res. 2017; 23(14):3585-3591. DOI: 10.1158/1078-0432.CCR-16-2375. View