Ripretinib Exhibits Better Tolerability Profile Vs Sunitinib in Advanced GIST Tumors

Ripretinib (Qinlock) may be more tolerable than sunitinib (Sutent) in patients with advanced gastrointestinal stromal tumors (GIST) whose disease has progressed following imatinib (Gleevec), according to an analysis of patient-reported outcomes (PROs) presented during the 2022 ASCO Annual Meeting. Although progression-free survival (PFS) was similar between the 2 agents according to data from the phase 3 INTRIGUE trial (NCT03673501), patients who received ripretinib had fewer total number of days with grade 3 or worse treatment-related toxicities and significantly less physical decline symptoms.

Overall, 24% of patients receiving ripretinib experienced at least 1 grade 3 or worse treatment-emergent adverse event (TEAE) compared with 51% of those receiving sunitinib. In addition, the mean number of days patients experienced a grade 3 or worse TEAE was 11 days with ripretinib vs 42 days with sunitinib (P < .0001). Among patients who experienced a grade 3 or greater TEAE, the mean number of days was 48 days vs 81 days, respectively.

“Despite not meeting the primary end point of superior PFS, ripretinib may provide meaningful benefit to patients with advanced GIST previously treated with imatinib,” study authors wrote in the poster.

Ripretinib is a switch-control kinase inhibitor approved to treat patients with advanced GIST tumors.

INTRIGUE randomly assigned patients with advanced GIST whose disease had either progressed beyond, or were intolerant to, imatinib, 1:1 to receive ripretinib (n = 223) once daily at 150 mg or sunitinib (n = 221) once daily at 50 mg on a 4-weeks-on, 2-weeks-off regimen. Treatment was administered in a 42-day cycle until discontinuation. To manage toxicities, providers were allowed to modify dosage in accordance with the package insert or institutional guidance, in the case of sunitinib, or at investigator discretion per protocol outlined dose modification, in the case of ripretinib.

Using the EORTC QLQ-C30 and Dermatology Life Quality Index, investigators assessed the PROs reported in the clinical trial. Data were collected on days 1, 15, and 29 of cycle 1, and on days 1 and 29 of all other cycles. Investigators estimated minimum clinically important differences using half of a standard deviation of the response at baseline.

PRO completion rates were similar between the 2 arms. Except for constipation, patients receiving ripretinib reported superior outcomes for all commonly observed TEAEs. Patients in the ripretinib arm also reported significantly less diarrhea, fatigue, appetite loss, nausea and vomiting, and pain, compared with sunitinib, at many follow-up assessments. These patients also demonstrated significantly less decline in role function and physical function at multiple assessments.

Notably, patients receiving ripretinib experienced less impactful skin toxicities than those treated with sunitinib. Upwards of 35% percent of patients treated with sunitinib reported that skin toxicities as having a moderate impact compared with less than 25% of patients receiving ripretinib. Similarly, more than 20% of patients treated with sunitinib experienced skin toxicities that had a very large impact on their quality of life vs less than 10% of those in the ripretinib arm.

“Moderate or severe effect of skin toxicity on patient quality of life as measured by DLQI was more commonly experienced in patients in the sunitinib arm vs patients in the ripretinib arm,” the study authors wrote.

Reference

Gelderblom H, Jones RL, Blay JY, et al. Patient reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after imatinib in INTRIGUE, a phase 3 open-label study. J Clin Oncol. 2022;40(suppl 16):11541. doi:10.1200/JCO.2022.40.16_suppl.11541