Testing for anaplastic lymphoma kinase rearrangement to target crizotinib therapy: oncology, pathology and health economic perspectives

Abstract

Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer. The therapy was approved by the US FDA in August 2011 and received conditional marketing approval by the European Commission in October 2012 for advanced non-small-cell lung cancer. A break-apart FISH-based assay was jointly approved with crizotinib by the FDA. This assay and an immunohistochemistry assay that uses a D5F3 rabbit monoclonal primary antibody were also approved for marketing in Europe in October 2012. While ALK rearrangement has relatively low prevalence, a clinical benefit is exhibited in more than 85% of patients with median progression-free survival of 8–10 months. In this article, the authors summarize the therapy and alternative test strategies for identifying patients who are likely to respond to therapy, including key issues for effective and efficient testing. The key economic considerations regarding the joint companion diagnostic and therapy are also presented. Given the observed clinical benefit and relatively high cost of crizotinib therapy, companion diagnostics should be evaluated relative to response to therapy versus correlation alone whenever possible, and both high inter-rater reliability and external quality assessment programs are warranted.

Keywords::

• companion diagnostic
• crizotinib
• FISH
• immunohistochemistry
• non-small-cell lung cancer

Financial & competing interests disclosure

J Lee served as a paid consultant to Abbott Laboratories and the health economic analysis was sponsored by Abbott Molecular. L Bubendorf has served as paid consultant to Pfizer and Abbott Molecular and he has received financial research support from Abbott Molecular. R Stahel has served as a paid consultant to Pfizer and Abbott Laboratories. S Peters has served as a paid consultant to Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Appendix A

Sample health economic and outcomes analysis calculations

This appendix provides example calculations to obtain the results presented in Table 4 of the manuscript. Tables 2 & 3 are replicated here, with the addition of an assigned variable used to present the calculations, and explicit references.

Table 2A. Health economic and outcome model baseline assumptions for all test strategies.

Table 3A. Alternative test strategies and associated test performance.

Table A-1. Outcomes for calculating the probability and net benefit of each strategy.

Example calculations of the net benefit minus cost for the IHC D5F3 strategy are presented in Table A-2:

Table A-2. Example net benefit calculations for the IHC D5F3 strategy.