Implementing precision cancer medicine in the public health services of Norway: the diagnostic infrastructure and a cost estimate

Anne Hansen Ree, Hege G Russnes, Daniel Heinrich, Svein Dueland, Kjetil Boye, Vigdis Nygaard, Laxmi Silwal-Pandit, Olga Østrup, Eivind Hovig, Vegard Nygaard, Einar A Rødland, Sigve Nakken, Janne T Øien, Christin Johansen, Inger R Bergheim, Veronica Skarpeteig, Menaka Sathermugathevan, Torill Sauer, Marius Lund-Iversen, Klaus Beiske, Salah Nasser, Lars Julsrud, Claudius H Reisse, Espen A Ruud, Vivi Ann Flørenes, Kirsten T Hagene, Eline Aas, Hilde Lurås, Siv Johnsen-Soriano, Gry A Geitvik, Ole Christian Lingjærde, Anne-Lise Børresen-Dale, Gunhild M Mælandsmo, Kjersti Flatmark, Anne Hansen Ree, Hege G Russnes, Daniel Heinrich, Svein Dueland, Kjetil Boye, Vigdis Nygaard, Laxmi Silwal-Pandit, Olga Østrup, Eivind Hovig, Vegard Nygaard, Einar A Rødland, Sigve Nakken, Janne T Øien, Christin Johansen, Inger R Bergheim, Veronica Skarpeteig, Menaka Sathermugathevan, Torill Sauer, Marius Lund-Iversen, Klaus Beiske, Salah Nasser, Lars Julsrud, Claudius H Reisse, Espen A Ruud, Vivi Ann Flørenes, Kirsten T Hagene, Eline Aas, Hilde Lurås, Siv Johnsen-Soriano, Gry A Geitvik, Ole Christian Lingjærde, Anne-Lise Børresen-Dale, Gunhild M Mælandsmo, Kjersti Flatmark

Abstract

Objective: Through the conduct of an individual-based intervention study, the main purpose of this project was to build and evaluate the required infrastructure that may enable routine practice of precision cancer medicine in the public health services of Norway, including modelling of costs.

Methods: An eligible patient had end-stage metastatic disease from a solid tumour. Metastatic tissue was analysed by DNA sequencing, using a 50-gene panel and a study-generated pipeline for analysis of sequence data, supplemented with fluorescence in situ hybridisation to cover relevant biomarkers. Cost estimations compared best supportive care, biomarker-agnostic treatment with a molecularly targeted agent and biomarker-based treatment with such a drug. These included costs for medication, outpatient clinic visits, admission from adverse events and the biomarker-based procedures.

Results: The diagnostic procedures, which comprised sampling of metastatic tissue, mutation analysis and data interpretation at the Molecular Tumor Board before integration with clinical data at the Clinical Tumor Board, were completed in median 18 (8-39) days for the 22 study patients. The 23 invasive procedures (12 from liver, 6 from lung, 5 from other sites) caused a single adverse event (pneumothorax). Per patient, 0-5 mutations were detected in metastatic tumours; however, no actionable target case was identified for the current single-agent therapy approach. Based on the cost modelling, the biomarker-based approach was 2.5-fold more costly than best supportive care and 2.5-fold less costly than the biomarker-agnostic option.

Conclusions: The first project phase established a comprehensive diagnostic infrastructure for precision cancer medicine, which enabled expedite and safe mutation profiling of metastatic tumours and data interpretation at multidisciplinary tumour boards for patients with end-stage cancer. Furthermore, it prepared for protocol amendments, recently approved by the designated authorities for the second study phase, allowing more comprehensive mutation analysis and opportunities to define therapy targets.

Keywords: cost model; metastasis; molecularly targeted therapy; mutation profiling; public health services.

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
The study mechanics. AE, adverse events; ATI, actionable target identification; CTB, Clinical Tumor Board; MTB, Molecular Tumor Board.
Figure 2
Figure 2
The diagnostic infrastructure. FISH, fluorescence in situ hybridisation; seq., sequencing.
Figure 3
Figure 3
The 22 study patients: overall survival (first patient enrolled 9 May 2014, last patient enrolled 26 August 2015, censoring date 9 May 2016); primary tumour sites; detected mutations in metastatic tumour samples.

References

    1. Tannock IF, Hickman JA. Limits to personalized cancer medicine. N Engl J Med 2016;375:1289–94.10.1056/NEJMsb1607705
    1. Jameson JL, Longo DL. Precision medicine-personalized, problematic, and promising. N Engl J Med 2015;372:2229–34.10.1056/NEJMsb1503104
    1. Robinson JT, Thorvaldsdóttir H, Winckler W, et al. . Integrative genomics viewer. Nat Biotechnol 2011;29:24–6.10.1038/nbt.1754
    1. Yang H, Wang K. Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR. Nat Protoc 2015;10:1556–66.10.1038/nprot.2015.105
    1. Scheie D, Andresen PA, Cvancarova M, et al. . Fluorescence in situ hybridization (FISH) on touch preparations: a reliable method for detecting loss of heterozygosity at 1p and 19q in oligodendroglial tumors. Am J Surg Pathol 2006;30:828–37.10.1097/01.pas.0000213250.44822.2e
    1. Von Hoff DD, Stephenson JJ, Rosen P, et al. . Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol 2010;28:4877–83.10.1200/JCO.2009.26.5983
    1. Niraula S, Amir E, Vera-Badillo F, et al. . Risk of incremental toxicities and associated costs of new anticancer drugs: a meta-analysis. J Clin Oncol 2014;32:3634–42.10.1200/JCO.2014.55.8437
    1. Hovelson DH, McDaniel AS, Cani AK, et al. . Development and validation of a scalable next-generation sequencing system for assessing relevant somatic variants in solid tumors. Neoplasia 2015;17:385–99.10.1016/j.neo.2015.03.004

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