Ripretinib Yields Clinically Meaningful Benefit in Advanced GIST

Patients who crossed over from receiving placebo to ripretinib for advanced gastrointestinal stromal tumors (GIST) in the INVICTUS trial had improved progression-free survival (PFS) and overall survival (OS), according to data analyses presented at the virtual 2020 ESMO World Congress on Gastrointestinal (GI) Cancer.

“Ripretinib is a novel switch-control tyrosine kinase inhibitor (TKI) that broadly inhibits KIT and PDGFRA kinase signaling through a dual mechanism of action,” wrote Cesar Serrano, MD, Vall d’Hebron Institute of Oncology, Barcelona, Spain, and colleagues on the background of the randomized, phase 3 INVCTUS Trial.

While presenting analyses from the INVICTUS trial at the ESMO World Congress on GI Cancer, Dr Serrano explained that primary mutations in KIT of PDGFRA occur in 85% of patients with GIST.

In INVICTUS, total of 129 patients were randomized in a 2:1 ratio to receive ripretinib (n = 85) or placebo (n = 44). Patients entered the open-label phase of the study when they had disease progression after treatment, and those treated with placebo were given the opportunity to cross over to the ripretinib arm.

The primary end points of the study were PFS by blinded independent central review after crossover, as well as OS.

The median PFS was 4.6 months for patients who crossed over to ripretinib therapy versus 1.0 month for patients in the initial placebo arm and 6.3 months in the initial ripretinib arm.

The median OS for patients who crossed over was 11.6 months versus 1.8 months with placebo (no crossover) and 15.1 months in patients initially randomized to receive ripretinib.

Compared with placebo, ripretinib improved PFS and OS by 85% and 64%, respectively, in patients with 4th-line advanced GIST.

“This is actually the first time that a TKI shows an OS benefit in imatinib-resistant GIST,” Dr Serrano told attendees.

No new safety signals were observed.

“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,” stated Dr Serrano.

“These data suggest that for patients who were able to crossover, ripretinib established active disease control despite delayed initiation of treatment; however, maximum benefit is achieved when ripretinib is used immediately after failure of prior therapy in patients 4th line advanced GIST,” he concluded.—Kaitlyn Manasterski