ASCO 2025: Expert Perspectives in Gastrointestinal Stromal Tumor Treatment - Episode 5
Ripretinib Use in Advanced Gastrointestinal Stromal Tumors
Panelists discuss how most gastrointestinal stromal tumor (GIST) patients can tolerate approved agents with proper adverse effect management, the efficacy data from the INVICTUS and INTRIGUE trials that led to ripretinib's approval, and the unique adverse effects such as alopecia that distinguish ripretinib from other therapies.
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The treatment of patients with GIST involves carefully balancing treatment efficacy with tolerability across multiple therapeutic lines. Most patients can successfully tolerate approved GIST medications through proactive adverse effect management, particularly addressing challenging complications such as hand-foot syndrome associated with sunitinib and regorafenib. Health care providers utilize comprehensive approaches including proper skin moisturization, friction avoidance, urea cream application, and dermatology consultations to maintain patients on optimal therapies. Cannabis has emerged as an interesting consideration in the NCCN guidelines for patients with true intolerance to certain agents.
Ripretinib represents a significant advancement in fourth-line GIST treatment, demonstrating superior tolerability compared with earlier generation therapies. The INVICTUS trial data revealed impressive efficacy with median progression-free survival of 6.3 months vs 1 month for placebo, along with opportunities for dose escalation in patients experiencing progression. While ripretinib causes unique alopecia patterns that change hair texture and appearance, quality-of-life measures showed improvement despite this cosmetic adverse effect. The drug requires specific monitoring considerations, including echocardiogram surveillance and dermatology involvement for potential cutaneous findings.
The INTRIGUE trial provided crucial insights into optimal drug sequencing strategies for patients with GIST progressing after imatinib therapy. This open-label randomized study comparing sunitinib to ripretinib showed similar median progression-free survival of approximately 8 months across all patients. However, subgroup analyses revealed important mutation-specific efficacy patterns, with exon 11 primary mutations and exon 9 mutations showing differential responses to specific agents. These findings are driving current clinical trials investigating personalized treatment approaches based on individual patient mutation profiles, representing a paradigm shift toward precision medicine in GIST management.
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