Prevalence of gastrointestinal stromal tumour (GIST) in the United Kingdom at different therapeutic lines: an epidemiologic model

Abstract

Background: The prevalence of patients with gastrointestinal stromal tumourgst (GIST) who fail currently available treatments imatinib and sunitinib (third-line treatment-eligible GIST) is unknown, but is expected to be below an ultra-orphan disease threshold of 2/100,000 population used in England and Wales. Our study was designed to estimate the prevalence and absolute number of UK patients with unresectable/metastatic GIST at first-, second- and eventually third-line treatment.

Methods: Our open population model estimates the probability that the prevalence of UK third-line treatment-eligible GIST patients will remain under the ultra-orphan disease threshold. Model parameters for incidence, proportion of unresectable/metastatic disease and survival estimates for GIST patients were obtained from a targeted literature review and a UK cancer register. The robustness of the results was checked through differing scenarios taking extreme values of the input parameters.

Results: The base-case scenario estimated a prevalence of third-line treatment-eligible GIST of 1/100,000 and a prevalence count of 598 with a 99.9% likelihood of being below the ultra-orphan disease threshold. The extreme scenarios, one-way and probabilistic sensitivity analyses and threshold analysis confirmed the robustness of these results.

Conclusions: The prevalence of third-line treatment-eligible GIST is very low and highly likely below the ultra-orphan disease threshold.

Figure 1

Model to assess GIST patient prevalence in the UK at different treatment stages. GIST = gastrointestinal stromal tumour; TTT = time to transition; UK = United Kingdom. The model parameters are given in Table 1. Z₁ refers to the total UK population and is fixed in all calculations at 62,262,000. Z₂ is the number of patients with non-metastatic GIST who have been resected and are currently recurrence free. Z₃ is the number of patients with non-resectable metastatic GIST and who are currently progression free while receiving treatment with imatinib. Similarly, Z₄ and Z₅ are the numbers of patients who are progression-free while receiving sunitinib and a third-line treatment, respectively. γ₂ is the annual rate of relapse which is estimated from the duration of relapse-free survival in this state. γ₃ is the annual rate of failure calculated from the duration of PFS and TTP on imatinib. γ₄ is the annual rate of failure calculated from the duration of PFS and TTP on sunitinib. γ₅ is the annual probability of failure calculated from the duration of OS on a range of investigational third-line treatments or best supportive care. Γ = incidence of newly diagnosed GIST. p = proportion.

Figure 2

Tornado diagram: Univariate sensitivity analysis for base-case scenario (low incidence and short third-line treatment-eligible GIST survival). GIST = gastrointestinal stromal tumour; TTT = time to transition.