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O-13 Efficacy and safety of ripretinib as ≥4th-line therapy for patients with gastrointestinal stromal tumor following crossover from placebo: Analyses from INVICTUS

2020; Elsevier BV; Volume: 31; Linguagem: Inglês

10.1016/j.annonc.2020.04.066

1569-8041

César Serrano, Michael C. Heinrich, Suzanne George, John Zalcberg, Sebastian Bauer, Hans Gelderblom, Patrick Schöffski, Robin L. Jones, Steven Attia, Gina Z. D’Amato, Ping Chi, Peter Reichardt, J. Meade, V. Reichert, Kelvin Shi, Jean‐Yves Blay, Margaret von Mehren,

Gastric Cancer Management and Outcomes

Ripretinib is a novel switch-control tyrosine kinase inhibitor (TKI) that broadly inhibits KIT and PDGFRA kinase signaling through a dual mechanism of action. In INVICTUS, a randomized, double-blind, placebo-controlled trial of ripretinib in ≥4th-line advanced gastrointestinal stromal tumor (GIST), ripretinib reduced the risk of disease progression or death by 85% vs placebo and had a favorable overall safety profile. In the double-blind period, patients with advanced GIST previously treated with at least imatinib, sunitinib, and regorafenib were randomized (2:1) to ripretinib 150 mg QD or placebo. Upon disease progression (PD) as determined by blinded independent central review (BICR), patients entered the open-label phase of the study. Patients who were on placebo were given the opportunity to cross over to open-label ripretinib 150 mg QD. Progression-free survival (PFS) by BICR after crossover and overall survival (OS) were evaluated. Treatment-emergent adverse events (TEAEs) were graded using CTCAE v4.03. Overall, 129 patients were randomized and 128 received treatment (85 ripretinib 150 mg QD; 43 placebo) in the double-blind phase. As of the data cutoff (31 May 2019), 29 patients crossed over from placebo to open-label ripretinib 150 mg QD after PD was confirmed by BICR. There were 15 patients initially randomized to the placebo arm who did not crossover (majority due to PD or death). Patients that crossed over to ripretinib 150 mg QD had a median PFS of 4.6 months (95% CI, 1.8–NE) compared with 6.3 months seen in the initial ripretinib arm and compared with 1.0 month seen in the initial placebo arm. Additionally, there were two patients with confirmed partial responses after crossover to ripretinib. Median OS in patients who crossed over to ripretinib was 11.6 months, compared with 15.1 months in patients initially randomized to ripretinib and 1.8 months in patients on placebo who did not crossover. Based on the review of safety data, no new safety signals emerged from the crossover population that were not already observed in patients in the initial ripretinib arm. In the phase 3, randomized INVICTUS trial, patients exhibited a clinically meaningful benefit from ripretinib after crossover from placebo and had a safety profile that was generally consistent with previously reported data from the double-blind period. The median PFS of patients who crossed over was numerically lower than was observed in the ripretinib arm during the initial double-blind period. Patients in the placebo arm that failed to crossover had an increased risk of fatal disease progression. These data suggest that timely treatment with ripretinib may provide improved outcomes in patients with ≥4th-line advanced GIST.