Long-term survivorship challenges of advanced/metastatic GIST patients responding to Tyrosine Kinase Inhibitor Treatment: An observational study

Gastrointestinal stromal tumours (GISTs) represent a rare family of diseases arising anywhere along the gastrointestinal tract. The mainstay of therapy for patients with localized GIST is surgical resection, which is curative in about half of patients. The development of targeted agents known as tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis of non-operable advanced/metastatic GIST patients. Today, 10-15 % of TKI treated patients with advanced or metastatic GIST are still responding after 10 years of treatment. Because of the extended survival and the increasing group of patients with GIST who live with an advanced stage of a rare cancer with a more or less chronic perspective, it becomes more relevant to assess treatment effectiveness both in terms of objective outcomes (e.g. survival) and in terms of subjective patient reported outcomes including health-related quality of life (HRQoL) to determine the net clinical benefit of GIST treatment. Studies specifically investigating the experiences of the long-term survivors with metastatic GIST who are using TKI for at least 5 years are lacking.

The study aims at setting up a prospective database of patients who have been on TKI treatment for at least 5 years and documenting the follow-up treatment. This registry will provide a unique opportunity to collect information to describe the HRQoL survivorship challenges these patients are facing. This study consist of 3 parts.

Part 1. Develop an item list with HRQoL issues of relevance for GIST patients with advanced/metastatic disease on TKI.

A search of the literature was performed to identify all relevant HRQoL issues for GIST patients. Interviews were conducted with GIST patients on long term (>5 years) TKI treatment (N=15) and health care professionals (HCPs) (N=10). A complete list of HRQoL issues was consolidated into a comprehensive list of issues.

This list of HRQoL issues was presented to GIST patients (N=45) from the Netherlands, Norway, UK, Germany and Hong Kong. Patients were asked to rate the HRQoL issues on relevance and importance, and to indicate relevant missing issues. The data of this pilot test has been analysed according to the EORTC module development guidelines and a final list of HRQoL issues has been created.

Part 2. Retrospective observational cohort – Test the item list and applicability of the EORTC QLQ-C30 among GIST patients with metastatic disease on TKI.

Inclusion criteria: patients with advanced or metastasized GIST who have been treated with TKI for five years or longer.

Estimated number of patients: 75-100.

Part 3. Prospective observational cohort (2-year recruitment) – Determine the prevalence of HRQoL problems, risk factors for HRQoL problems and the course of HRQoL problems over time among GIST patients with metastatic disease on TKI.

Inclusion criteria: patients with advanced or metastasized GIST who have been treated with first and second line TKI for at least 2 years.

We estimate to be able to include 330 patients. According to the sample size calculation we need a minimum of 228 patients.

Data collection for both parts will be done

Online via Castor.

Part 2: once after registration.

Part 3: every year, and in case of disease progression and/or treatment switch. Follow-up: 10 years

Criteria of evaluation:

HRQoL

• Item List
• EORTC QLQ-C30
• EORTC QLQ-SURV100
• EQ-5D-5L

Efficacy

• Overall survival, progression free survival, tumour response.

Safety

• Adverse events (CTCAE v5.0) by HCPs

Other study parameters:

• Patient characteristics, tumour characteristics and treatment characteristics
• Laboratory results
• Reasons for cessation of TKI treatment
• Coping with medical situations
• Illness cognition questionnaire
• Financial toxicity
• WISP

The item list is finalized and ready to be applied in part 2 and 3. Ethical approval is obtained and recruitment has started.

Start of phase 2 and 3 of the study.

Recruitment at the coordinating site began at the end of May, and 16 patients have already been included. The Royal Marsden Hospital has also initiated recruitment and has enrolled 10 patients to date. In addition, Hospital Clínico San Carlos is ready to commence recruitment.

September 2025-December 2026: obtain ethical approval in collaborating sites and start recruitment there for phase 2 and 3.

We are still open for new collaborators for phase 2 and 3 of this study.

This study specifically investigates the experiences of the long-term survivors with advanced or metastatic GIST who are using tyrosine kinase inhibitors (TKI) for a long duration.