Researchers have discovered that intrapatient dose escalation (IPDE) of ripretinib after disease progression provides clinically beneficial outcomes in patients with advanced gastrointestinal stromal tumor (GIST), according to a study published in the European Journal of Cancer.

Ripretinib is 1 of 5 tyrosine kinase inhibitors (TKIs) approved for use in the US for GIST. At present, it is the fourth-line TKI therapy after imatinib (adjuvant and first-line), sunitinib (second-line), and regorafenib (third-line). Therefore, ripretinib is used in patients with advanced GIST who have been treated with 3 or more TKIs. 

In this study, researchers reported the results of a phase 1 study of IPDE in patients with GIST treated across second, third, and later lines of therapy. Participants were aged at least 18 years with a histologically confirmed GIST diagnosis and more than 1 measurable lesion. They also had a KIT or PDGFRA mutation, and they had experienced intolerability or progressed onto at least one line of TKIs. Eligible patients were given ripretinib (150 mg) once a day. When they experienced disease progression, they were given the option to escalate their daily ripretinib dose to 150 mg twice a day. 

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Of the 142 eligible patients, 67 chose to escalate their ripretinib dose from 150 mg once a day to 150 mg twice a day after disease progression. The results were measured in terms of progression-free survival (PFS2) from the date of IPDE until disease progression or death. 

The results showed positive clinical outcomes for patients who chose IPDE across all lines of therapy. For patients on second-line therapy, the median PFS2 was 5.6 months. For patients on third-line therapy, the median PFS2 was 3.3 months. For patients on fourth-line therapy or later, the median PFS2 was 4.6 months. In addition, ripretinib was found to have an acceptable safety profile and was well tolerated. 

The results of this study show that ripretinib dose escalation is efficacious in improving clinical outcomes for a wide range of patients with advanced GIST. The main limitation of this trial is that not every participant who experienced disease progression chose IPDE, thus limiting the sample size. 


George S, Chi P, Heinrich MC, et al. Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour. Eur J Cancer. Published online August 12, 2021. doi:10.1016/j.ejca.2021.07.010