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Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor:
John R Zalcberg1,2, Michael C Heinrich3, Suzanne George4
1School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
Background:
Ripretinib 150 mg once daily (QD) is indicated for advanced gastrointestinal stromal tumors (GISTs) as at least fourth-line therapy. In INVICTUS, ripretinib intrapatient dose escalation (IPDE) to 150 mg b.i.d. was allowed after progressive disease (PD) on 150 mg QD by blinded independent central review using modified RECIST 1.1. We report the efficacy and safety of ripretinib IPDE to 150 mg b.i.d. after PD among patients randomized to ripretinib 150 mg QD in the INVICTUS study.
Materials And Methods:
Tumor imaging was performed every 28-day cycle for the first four cycles in the ripretinib 150 mg QD period and then every other cycle, including the 150 mg b.i.d.
Period:
Among the ripretinib IPDE patients, progression-free survival (PFS)1 was the time from randomization until PD; PFS2 was the time from the first dose of ripretinib 150 mg b.i.d. to PD or death.
Results:
Among 43 ripretinib IPDE patients, median PFS1 was 4.6 months (95% confidence interval [CI], 2.7-6.4) and median PFS2 was 3.7 months (95% CI, 3.1-5.3). Median overall survival was 18.4 months (95% CI, 14.5-not estimable). Ripretinib 150 mg b.i.d. (median duration of treatment 3.7 months) was well tolerated with new or worsening grade 3-4 treatment-emergent adverse events (TEAEs) of anemia in six (14%) and abdominal pain in three (7%) patients. Ripretinib 150 mg b.i.d. was discontinued because of TEAEs in seven (16%) patients.
Conclusion:
Ripretinib 150 mg b.i.d. after PD on 150 mg QD may provide additional clinically meaningful benefit with an acceptable safety profile in patients with at least fourth-line GISTs.
Implications For Practice:
Of the 85 patients with advanced gastrointestinal stromal tumor having received at least three prior anticancer therapies randomized to ripretinib 150 mg once daily (QD) in the phase III INVICTUS study, 43 underwent ripretinib intrapatient dose escalation (IPDE) to 150 mg b.i.d. after progressive disease (PD). Median progression-free survival was 4.6 months before and 3.7 months after ripretinib IPDE. The safety profile of ripretinib 150 mg b.i.d. was acceptable. These findings indicate ripretinib IPDE to 150 mg b.i.d. may provide additional clinical benefit in patients with PD on ripretinib 150 mg QD, for whom limited treatment options exist.
Insights
Ripretinib dose escalation to 150 mg twice daily (b.i.d.) after initial 150 mg once daily (QD) treatment showed acceptable safety in advanced gastrointestinal stromal tumors (GISTs). This strategy may offer additional clinical benefit for patients with progressive disease on ripretinib QD.
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced gastrointestinal stromal tumors (GISTs) often require later-line therapies.
- Ripretinib 150 mg once daily (QD) is approved as a fourth-line treatment for advanced GISTs.
Purpose of the Study:
- To evaluate the efficacy and safety of intrapatient dose escalation (IPDE) of ripretinib to 150 mg twice daily (b.i.d.) after progressive disease (PD) in patients with advanced GISTs.
- To assess the clinical benefit of ripretinib IPDE in a subgroup of patients from the INVICTUS study.
Main Methods:
- The INVICTUS study randomized patients with advanced GISTs to ripretinib 150 mg QD.
- Patients who experienced PD on 150 mg QD were allowed to escalate to ripretinib 150 mg b.i.d. (IPDE).
- Tumor imaging was conducted regularly to monitor disease progression.
Main Results:
- Among 43 patients who underwent IPDE, median progression-free survival (PFS1) before escalation was 4.6 months.
- Median PFS after escalation to ripretinib 150 mg b.i.d. (PFS2) was 3.7 months.
- The overall safety profile of ripretinib 150 mg b.i.d. was acceptable, with manageable treatment-emergent adverse events.
Conclusions:
- Ripretinib IPDE to 150 mg b.i.d. may offer additional clinical benefit for advanced GIST patients progressing on 150 mg QD.
- This dose escalation strategy provides a viable option for patients with limited treatment alternatives.
- The safety profile supports the use of ripretinib b.i.d. in this setting.
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