Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study
Mené sur 43 patients atteints d'une tumeur stromale gastro-intestinale de stade avancé, cet essai randomisé évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du riprétinib avec escalade de dose, après la progression de la maladie
Background : Ripretinib 150 mg once daily (QD) is indicated for advanced gastrointestinal stromal tumor (GIST) as ≥fourth-line therapy. In INVICTUS, ripretinib intra-patient dose escalation (IPDE) to 150 mg twice daily (BID) 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 BID 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 4 cycles in the ripretinib 150 mg QD period and then every other cycle, including the 150 mg BID 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 BID 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 BID (median duration of treatment 3.7 months) was well tolerated with new or worsening Grade 3–4 TEAEs of anemia in 6 (14%) and abdominal pain in 3 (7%) patients. Ripretinib 150 mg BID was discontinued due to TEAEs in 7 (16%) patients. Conclusion : Ripretinib 150 mg BID after PD on 150 mg QD may provide additional clinically meaningful benefit with an acceptable safety profile in patients with ≥fourth-line GIST.