The study was evaluating a drug called ripretinib in patients with gastrointestinal stromal tumour who have progressed on the standard therapies of at least imatinib, sunitinib and regorafenib. We know that those patients don’t have any approved options, there are some things that have been assessed and patients may have tried or other clinical trials but it was really for those patients in whom there is no standard of care.
The study was designed as a placebo controlled study. The initial study phase was a blinded phase and patients were randomised two to one to the ripretinib versus placebo. We found that patients who started on ripretinib had a significant improvement in progression free survival compared to placebo. There was a reduction in terms of progression as well as death by 85%.
The implications are that this is an active drug. One of the things that we found that was surprising that even after patients progressed and were unblinded they were allowed to cross over but even with that design patients had an improvement in their overall survival being on ripretinib as their first line. Those patients that were able to cross over did have a benefit from placebo to ripretinib. The difference in overall survival for those patients was about two months for those patients who never crossed over to about a year for the patients who crossed over.
So all of this information suggests that ripretinib is a very active agent for patients in this line of therapy who have no active options. Hopefully as we move forward it will become available for patients in that space.
Most of the adverse events were grade 1 or 2 and what we would expect from tyrosine kinase inhibitors. One of the things that was unusual was alopecia or hair loss seen in about half of the patients. The hair loss happens but then hair does seem to grow back. In my experience in treating patients on this trial when it grows back it’s somewhat coarser and oftentimes curlier than the natural hair but that’s a difference. The other things that were seen were hand foot syndrome or PPE which we do see with some of the other approved agents. Compared to the other approved agents the consensus experience is that it is less intense than what is seen with some of the other drugs. There is less actual peeling of the skin, it’s more dryness. It’s real but very manageable and primarily grade 1 or 2 and not severe grade 3 toxicity.
From the perspective of thinking about patients who have progressed on standard therapy hopefully this will become an approved agent. Overall the toxicity profile was very manageable and similar to other agents with the exception of the alopecia. It hopefully will become a new standard of care for patients in that space.