The INVICTUS Trial in GIST: Study Design and Results

Transcript:

Jean-Yves Blay, MD, PhD: The phase III INVICTUS trial tested a new tyrosine kinase inhibitor called ripretinib versus placebo in patients with gastrointestinal stromal tumors with an imitation KIT PDGF receptor alpha, or in patients progressing in advanced phase after treatment with imatinib, sunitinib, and regorafenib. This is a population of patients with no other treatment options for whom the proposition of experimental treatment is usually what is recommended in clinical practice guidelines.

The study investigated the value of ripretinib versus placebo in the randomized double-blind setting: 2 to 1 randomization with central radiological review to investigate the primary endpoint, which was progression-free survival. The inclusion criteria were actually patients in good performance stage of 0 to 1 and patients with an advanced disease that had progressed on the 3 registered tyrosine kinase inhibitors, which we mentioned.

This study was performed worldwide with accrual in a large number of countries and included a bit more than 120 patients in less than 1 year. The results, which are going to be presented, focus on the primary endpoint for progression-free survival reviewed by blinded independent central review. And secondary endpoints are response rate, overall survival, quality of life, and safety.

The main message from the INVICTUS study was that ripretinib very significantly improves progression-free survival as compared with placebo: 1 month versus 6 months with ripretinib of progression-free survival. That was a primary endpoint and the P value is highly significant. When it comes to response rate, the response rate was also superior in the ripretinib arm: 0% in the placebo arm, 8% in the ripretinib arm. That was very interesting, I think, even though the statistical plan was quite complex. This is ambiguous to evaluate but the overall survival of patients treated with ripretinib reached a median of 15 months as compared with 6 months for patients treated in the placebo arm, even though there was a crossover.

That’s a very important message, that the primary endpoint was reached and that there was this very significant improvement in overall survival, which is as we all know a major parameter that drives the treatment of patients with advanced disease. This came at the price of a very well-tolerated agent, actually the adverse-effect profile and the safety were very comparable with what was expected, and the quality of life also proved to be very much in favor of the ripretinib arm. Overall a study that was very positive for all major endpoints, which are useful for the management of patients with advanced GISTs [gastrointestinal stromal tumors].

Transcript Edited for Clarity