Long-term Survivorship Challenges of Advanced/Metastatic GIST Patients Responding to Tyrosine Kinase Inhibitor Treatment: an Observational Study

Long-term Survivorship Challenges of Advanced/Metastatic GIST Patients Responding to Tyrosine Kinase Inhibitor Treatment: an Observational Study (EORTC-1944)

Gastrointestinal stromal tumours (GISTs) are rare malignancies arising along the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) have substantially improved survival for patients with unresectable or metastatic GIST. As a result, an increasing number of patients live with advanced disease under chronic TKI therapy, highlighting the need to understand long-term survivorship, including health-related quality of life (HRQoL), treatment burden, and clinical outcomes.

This international, multicentre observational study includes two components: a retrospective cross-sectional study to evaluate the relevance and applicability of patient-reported outcome instruments, and a prospective cohort to document long-term clinical outcomes, HRQoL, treatment patterns, and survivorship challenges.

Participants will include adults with advanced or metastatic GIST who have received TKI therapy for at least 2 years. Data will be collected from medical records and through validated patient-reported outcome questionnaires at baseline and annually for up to 10 years. This study aims to provide insight into HRQoL problems, treatment discontinuation, coping strategies, and the impact of financial toxicity among long-term survivors of GIST.

Gastrointestinal stromal tumour (GIST) is a rare malignancy for which long-term treatment with tyrosine kinase inhibitors (TKIs), particularly imatinib, has substantially improved survival. As a result, an increasing number of patients live with advanced or metastatic disease under chronic TKI therapy, highlighting the need to better understand long-term survivorship, including health-related quality of life (HRQoL), treatment burden, and clinical outcomes.

This study is an international, multicentre observational study consisting of two components:

1. a retrospective cross-sectional study and
2. a prospective observational cohort (registry).

Study design and population

The retrospective component includes patients with unresectable or metastatic GIST receiving long-term TKI treatment (≥5 years). This component aims to evaluate the relevance and applicability of patient-reported outcome (PRO) instruments and to identify GIST-specific survivorship issues.

The prospective cohort includes patients with advanced or metastatic GIST who have received TKI therapy for at least 2 years. Participants will be enrolled across multiple centres in Europe and China.

Data collection

Data collection includes both patient-reported outcomes and clinical data.

Patient-reported outcomes are collected using validated questionnaires and study-specific item lists assessing HRQoL, survivorship issues, coping, and financial impact.

Clinical data are extracted from medical records and include disease characteristics, treatment history, tumour response, survival outcomes, and adverse events.

Follow-up

In the prospective cohort, participants will complete questionnaires at baseline and at annual follow-up assessments for up to 10 years. Clinical data will be collected longitudinally in parallel with routine care.

For patients who discontinue TKI therapy, reasons for discontinuation and subsequent clinical outcomes, including possible re-initiation of treatment, will be documented.

Study objectives

The primary objective is to determine the prevalence, risk factors, and longitudinal course of HRQoL problems among patients with unresectable or metastatic GIST receiving TKI therapy.

Secondary objectives include identifying factors associated with prolonged treatment and survival, describing clinical practice patterns, assessing treatment satisfaction and discontinuation, and evaluating outcomes following TKI interruption and re-introduction.

Ethical considerations

This is a non-interventional study. Participants will receive standard of care only. Study procedures consist primarily of questionnaire completion and data collection from medical records, representing minimal risk. Participants may withdraw at any time. Although no direct clinical benefit is expected, the study aims to generate knowledge to improve survivorship care for patients with GIST.

Inclusion Criteria:

• Age 18 years or older (no upper age limit);
• Advanced or metastatic GIST, diagnosis of GIST must be histologically proven;
• Treated with TKIs (eg. sunitinib, regorafenib, avapritinib, ripretinib) for at least 2 years; TKI treatment ongoing; interruptions up to 3 months are allowed;
• Able to read and answer questionnaires;
• Able to provide informed consent.

Exclusion Criteria:

• Patients receiving TKI in an adjuvant treatment setting.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before inclusion the study.
• Patients who are too ill (death is imminent), as determined by the referring health care professional.