Investigators sought to evaluate the tolerability and response of patients with GIST treated outside clinical trials with ripretinib dose escalation, presented at the 2021 CTOS Annual Meeting.

“Randomized clinical trials (RCTs) focus on producing internally valid results with stringent adherence to protocol, but this may compromise external validity. Compared with RCTs, real world-data better reflects the clinical environments in which medical interventions are used, including demographics, comorbidities, adherence, and concurrent treatments. In this scenario, retrospective real-world data can complement the evidence generated by RCTs. Here we evaluate the tolerability and response of patients with GIST treated outside clinical trials with ripretinib dose escalation,” explains Philippos A. Costa, MD, University of Miami, alongside fellow investigators.

Researchers identified patients with locally advanced or metastatic GIST who received ripretinib at 150 mg QD/150 mg BID at a single center between 2019 and 2021. Following the review of clinicopathologic features, treatment adverse effects were recorded according to the Common Terminology Criteria for Adverse Events, and treatment responses were documented according to Choi’s criteria. Duration of response were calculated from the initiation of therapy until disease progression. PFS was estimated by the Kaplan-Meier method.

As a result, 8 patients between the ages of 25-72 years, with a median age of 59 at diagnosis, were identified. Among the 3 male and 5 female patients, the primary location was the stomach in 4 cases, small intestine in 3 cases, and unknown in 1 case. The median initial size at diagnosis was 15 cm, with a median mitotic index of 12.5 by HPF. Furthermore, mutation analysis disclosed kit exon 9 mutations in 2 patients and kit exon 11 in 6 patients. The median number of treatment lines prior to initiation of ripretinib 150mg QD was 3, and ECOG status was 0 in 5 patients and 1 in 3.

Reported adverse effects include alopecia, hand-foot syndrome, fatigue, abdominal pain, allergic reaction, anemia, anorexia, arthralgia, cramping, papulopustular rash, constipation, diarrhea, weight loss, chills, and skin hyperpigmentation.

To conclude, similar to the sub-analysis of the INVICTUS and phase I clinical trial, dose escalation of ripretinib yields objective responses in patients whose tumors progressed after standard dose. Moreover, dose escalation was also well tolerated with similar toxicity profile than daily dose. Future studies are needed to assess when dose escalation would be most appropriate: after progression on the standard dose, as a ripretinib re-challenge after a different agent, or even initially in a subset of patients harboring specific mutations or clinical characteristics. -Alexis Hyams