Ripretinib improves survival in patients with advanced gastrointestinal stromal tumours

Treatment with ripretinib provides a prolonged clinical and radiological benefit in patients with advanced gastrointestinal stromal tumours (GIST) within the expanded access program (EAP) in the UK, as shown in a study presented at the ESMO Sarcoma and Rare Cancers Congress 2023 in Lugano, Switzerland.

This finding is consistent with the recently reported phase III INTRIGUE and INVICTUS clinical trials, according to the researchers, led by Andrea Napolitano from The Royal Marsden Hospital (Chelsea) - NHS Foundation Trust, London, UK.

“Patients with GIST have limited treatment options once they have developed resistance to standard therapies,” said the researchers, who then examined the treatment outcomes in patients prescribed ripretinib, a novel tyrosine kinase inhibitor, as part of the EAP.

Napolitano and her team used The Royal Marsden Hospital database to carry out a retrospective review of patients with advanced GIST who initiated EAP ripretinib between January 2020 and October 2021. They used the Kaplan-Meier method to construct survival curves and conducted both univariate and multivariate Cox regression analyses. R Statistical Software was used to perform all analyses.

Forty-five patients with advanced GIST participated in the study and provided the following baseline data: sex, age, primary mutation type and tumour site, number and type of metastatic sites, ECOG performance status, and previous lines of therapy.

The median progression-free survival (PFS) with ripretinib 150 mg once daily was 7.4 (95 percent confidence interval [CI]) months over a median follow-up of 21.5 (95 percent CI, 19.0‒28.2) months. Twenty-three patients with disease progression received ripretinib 150 mg twice daily, which resulted in a median PFS of 5.9 (95 percent CI, 3.5‒9.2) months. [ESMO Sarcoma 2023, abstract 80P]

Overall, total PFS was 12.2 (95 percent CI, 7.9‒17.6) months, while the overall survival (OS) was 14.0 (95 percent CI, 9.9‒NA) months.

Multivariable analysis revealed better prognosis in patients who presented with a primary KIT exon 11 mutation. On the other hand, no association was observed between the number of previous lines of treatment and survival outcomes on ripretinib.

Notably, the best responses to ripretinib once- and twice-daily dosing were partial response (26.7 percent and 8.7 percent, respectively) and stable disease (46.7 percent and 34.8 percent, respectively).

These findings were supported by those from another study presented at ESMO 2023, this time among Chinese patients with advanced GIST.

Fourth-line treatment with ripretinib demonstrated profitable efficacy and safety. In addition, dose escalation could be beneficial for patients with poor response to ripretinib 150 mg once daily. [ESMO Sarcoma 2023, abstract 85P]

Specifically, 12 patients with advanced GIST received ripretinib intrapatient dose escalation (IPDE). The median PFS from treatment initiation to disease progression was 6.4 months, while that from dose escalation to progressive disease or death was 11 months. The median OS was not reachd in this study.

Ripretinib 150 mg once daily and IPDE were both well tolerated, the investigators noted.