When Treatment Options Run Out, Consider a Higher Drug Dose in GIST

In patients with advanced gastrointestinal stromal tumors, a dose escalation of Qinlock after recommended treatment with the agent may be the best next step, answering for the lack of a next approved agent after Qinlock.

With no current approved agent to be used in patients with advanced gastrointestinal stromal tumors (GIST) after Qinlock (repretinib), physicians should feel confident increasing the dosage, says an expert from Oregon Health Sciences University in reference to recent findings from the phase 3 INVICTUS study.

“If you look at professional guidelines, like (the National Comprehensive Cancer Network) NCCN or (the European Society for Medical Oncology) ESMO, which are the big professional cancer guidelines that doctors look at, they would suggest a lot of potential drugs based on the kind of limited data of phase 2 studies, some of which are quite small,” said Dr. Michael Heinrich, professor of medicine at Oregon Health Sciences University and one of the study authors, in an interview with CURE®.

With a dose escalation of Qinlock, patients did not experience any major toxicities or changes in side effects.

“Efficacy wise, I think it's a reasonable choice,” said Heinrich. “And I think the other part of it is that if you're tolerating the drug at the standard dose, these data give us some confidence that that's probably not going to change if you increase the dose. Switching to a different drug, side effects might be different or better, but they might be more. And so that's sort of the uncertainty.”

The data was presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Transcription:

Well, you know, this is sort of a knowledge gap. We don't have an approved agent after repretinib for advanced GIST, and so if you look at professional guidelines, like (the National Comprehensive Cancer Network) NCCN or (the European Society for Medical Oncology) ESMO, which are the big professional cancer guidelines that doctors look at, they would suggest a lot of potential drugs based on the kind of limited data of phase 2 studies, some of which are quite small. I think that this, as I said, the progression free survival, once you dose escalated was 3.7 months, which is not as long as we would like, obviously, but it is competitive for anything else out there. So, you know, efficacy wise, I think it's a reasonable choice.

And I think the other part of it is that if you're tolerating the drug at the standard dose, these data give us some confidence that that's probably not going to change if you increase the dose. Switching to a different drug, side effects might be different or better, but they might be more. And so that's sort of the uncertainty. So I think it's a little bit attractive as oncologists to say, ‘Hey, you're doing really well on this drug side effect wise, let's just double the dose because I think that you'll continue to do well side effect wise and we can get some more benefit out of it.’ And we can also think, ‘What is our next option?’ It gives us a little bit more time to figure things out.”

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