Efficacy and Safety of Ripretinib in Advanced Gastrointestinal Stromal Tumors within an Expanded Access Program: A
Su Yin Lim1, Laura Ferro-López1, Elizabeth Barquin1
1The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Abstract:
Ripretinib, a novel tyrosine kinase inhibitor used in advanced gastrointestinal stromal tumors (GIST) resistant to standard therapies, was assessed in the United Kingdom (UK) within an Expanded Access Program (EAP). A retrospective review of patients treated between January 2020 and October 2021 within the ripretinib EAP in our Institution was conducted. Clinician-documented and mRECIST 1.1 assessments were collected. The primary endpoints were progression-free survival (PFS) and time to treatment discontinuation (TTD). Treatment beyond progression (TBP), overall survival (OS), objective response rates and safety data were also analyzed. Survival curves were constructed using the Kaplan-Meier method, and univariate and multivariate Cox regression analyses were performed. All analyses were performed with R software. Overall, forty-five patients were included. After a median follow-up of 24.2 (95% CI 19.7-29.7) months, the median PFS of the group receiving 150 mg ripretinib once daily (OD) was 7.9 (95% CI 5.6-19.3) months. In the cohort of 22 patients with dose escalation upon tumor progression to 150 mg ripretinib twice daily (BD), the median PFS from BD was 5.4 (95% CI 2.8-9.3) months. Overall, median PFS and OS values for patients on ripretinib were 9.7 (95% CI 8.3-18.1) and 14.0 (95% CI 9.9-NA) months, respectively. TTD was similar to PFS. TBP was observed in about one third of all patients. Objective responses to ripretinib OD and BD treatments were observed in 16.7% and 10.0% of the patients, respectively. No new safety signals were identified. In conclusion, patients with advanced GIST receiving ripretinib in the UK within the EAP reported prolonged benefits, in line with the recent phase III clinical trials.
Insights
Ripretinib provides prolonged progression-free survival (PFS) and overall survival (OS) in advanced gastrointestinal stromal tumors (GIST) patients. This tyrosine kinase inhibitor demonstrated a favorable safety profile in a UK Expanded Access Program (EAP).
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced gastrointestinal stromal tumors (GIST) often develop resistance to standard therapies.
- Ripretinib is a novel tyrosine kinase inhibitor targeting specific mutations in GIST.
- Expanded Access Programs (EAP) provide access to investigational drugs for patients with unmet needs.
Purpose of the Study:
- To assess the efficacy and safety of ripretinib in advanced GIST patients within a UK EAP.
- To evaluate progression-free survival (PFS), time to treatment discontinuation (TTD), and overall survival (OS).
- To analyze treatment beyond progression (TBP) and objective response rates (ORR).
Main Methods:
- Retrospective review of 45 GIST patients treated with ripretinib between January 2020 and October 2021.
- Data collected included clinician-documented assessments and mRECIST 1.1.
- Survival analyses utilized Kaplan-Meier method and Cox regression.
Main Results:
- Median PFS was 7.9 months for ripretinib 150 mg once daily (OD) and 5.4 months for escalated 150 mg twice daily (BD).
- Overall median PFS and OS were 9.7 and 14.0 months, respectively.
- Objective response rates were 16.7% (OD) and 10.0% (BD); no new safety signals were observed.
Conclusions:
- Ripretinib demonstrated prolonged clinical benefits in advanced GIST patients within the UK EAP.
- The safety profile was consistent with previous clinical trials.
- Ripretinib offers a valuable treatment option for GIST patients resistant to standard therapies.
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