Results from the phase 3 INVICTUS study in advanced gastrointestinal stromal tumors (GIST) were released at the virtual 2021 ESMO Congress to highlight significantly improved progress-free survival rates of ripretinib compared to placebo (PFS; 6.3 vs 1.0 month), reductions in risk of disease progression or death by 85%, and clinically meaningful improvements in median overall survival (OS; 15.1 vs 6.6 months).

The randomized, double-blind trial enrolled patients with advanced GIST who were treatment-naïve to either imatinib, sunitinib, and regorafenib. Inductions were randomized (2:1) to ripretinib 150 mg once daily (QD) or placebo under blinded independent review.

“Upon disease progression, patients on placebo could cross over to ripretinib 150 QD. All patients who received 150 mg QD and had radiological progression could receive 150 mg twice daily,” wrote Margaret von Mehren, MD, Fox Chase Cancer Center, Philadelphia, Pennsylvania, and co-investigators.

Mature data was made available on January 15, 2021, as a long-term update to previous primary INVICTUS data released on May 31, 2019 and presented at ESMO 2019.

129 patients with GIST were randomly assigned to either ripretinib or placebo, with 85 and 43 patients between both arms, respectively.

Patients randomized to ripretinib had a median PFS of 6.3 months (95% CI 4.6-8.1) versus 1.0 (95% CI 0.9-1.7) month for patients on placebo with a hazard ratio (HR) of 0.16. The median OS in those who received ripretinib was 18.2 months (95% CI 13.1-30.7) vs 6.3 (95% CI 4.1-10.0) months for placebo with a HR of 0.41.

Notably, there were no safety concerns observed with extensive exposure to ripretinib.

These evaluable data of primary and secondary endpoints confirm that 19 months after primary analysis, stable median PFS with no change since primary data release and improved median OS for patients received ripretinib.

 “These more mature data continue to support the clinically meaningful benefit in PFS and OS for ripretinib with an acceptable safety profile in patients with advanced GIST treated with 3 or more prior TKIs,” concluded Dr Mehren, et al. – Alexa Stoia