“In this, large, phase 3 trial, ripretinib was not found to be better than sunitinib in controlling gastrointestinal stromal tumour which has progressed on imatinib.
It is important to recognise that the side effect profile of ripretinib is more favourable with lower rates of hypertension, hand-foot skin reaction, and neutropenia.
This is an important factor in considering treating options for patients,” says Muhammad Shaalan Beg, MD, ASCO Expert in Gastrointestinal Cancer.
In patients with advanced gastrointestinal stromal tumours (GIST) that progressed on or were intolerant to imatinib, the efficacy of ripretinib was comparable to sunitinib.
These findings from the INTRIGUE trial were presented during the January session of the American Society of Clinical Oncology (ASCO) Plenary Series.
Approximately 80% of patients with GIST have primary mutations in KIT.
Imatinib is effective against KIT-mutated GIST, but the vast majority of patients with GIST will ultimately develop resistance to imatinib, most commonly due to the development of secondary mutations in KIT. Sunitinib is effective against some imatinib-resistant mutations.
In this international, multicenter study conducted in 122 active sites across 22 countries, 453 patients were randomized to ripretinib (226 patients; 163 with Exon 11) or sunitinib (227; 164 with Exon 11).
- Overall, median progression free survival (mPFS) for ripretinib was 8 months compared to 8.3 months for sunitinib. In patients with a KIT exon 11 primary mutation, mPFS for ripretinib was 8.3 months compared to 7 months for sunitinib arm (Hazard Ratio [HR] 0.88, p=0.360).
- The overall objective response rate (ORR) for ripretinib was 21.7% (49 patients) compared to 17.6% (40 patients) for sunitinib. In patients with a KIT exon 11 primary mutation, the ORR for ripretinib was 23.9% (39 patients) compared to 14.6% (24 patients) for sunitinib.
Ripretinib was generally well tolerated. Fewer patients in the ripretinib arm experienced grade 3-4 adverse events compared to sunitinib (41.3% vs 65.6%).
Patients receiving sunitinib were 3 times more likely to develop grade 3 hypertension compared with patients receiving ripretinib (26.7% vs 8.5%) and 7 times more likely to develop grade 3 hand-foot syndrome (a side effect of some chemotherapy treatments that can cause redness, swelling, and blistering on the palms of the hands and soles of the feet) compared to patients receiving ripretinib (10% vs 1.3%).
Fewer patients receiving ripretinib experienced a moderate to extremely large impact on their lives as measured by the Dermatology Life Quality Index.
Patients receiving ripretinib also experienced less deterioration in their ability to engage in either work or leisure activities during treatment.
“Even though the INTRIGUE study did not meet its primary endpoint of improved PFS, ripretinib and sunitinib efficacy appeared comparable. Although ripretinib was not superior to sunitinib as a second-line treatment for GIST, ripretinib has remarkable activity as a fourth-line or later agent and remains the only FDA-approved agent in this setting,” said lead author Michael C. Heinrich, MD, FACP.
“Our goal is to provide the full results of this study to the oncology community to help treating physicians make well-informed decisions on the best treatment for their patients with advanced GIST.”