Expanding the Use of Targeted Therapies in GIST

Neeta Somaiah, MD, an associate professor, and deputy department chair in the department of sarcoma medical oncology, division of cancer medicine at The University of Texas MD Anderson Cancer Center, discusses the continued role of the use of targeted therapies in treating patients with gastrointestinal stromal tumor (GIST).

According to Somaiah, the treatment of patients with GIST paved the way for the use of targeted therapies in oncology with the approval of imatinib (Gleevec) for patients with advanced or metastatic GIST in 2022. An accelerated approval was then granted in 2008 for the adjuvant use of imatinib in patients with resectable GIST, and in 2012, the use of this therapy continued for patients after a complete gross resection of CD117 GIST.

Now, several targeted therapies can be used for patients with GIST, such as sunitinib (Sutent) for patients where imatinib is no longer working or they cannot take it. Sunitinib targets the KIT and PDGFRA proteins, which imatinib does not, and helps to shrink and slow the growth of GIST. Furthermore, patients that fail imatinib and sunitinib can be put on regorafenib (Stivarga), which can help slow tumor growth. However, not enough research has shown if the drug can help patients live longer. Other drugs in the later-line settings include ripretinib (Qinlock) and avapritinib (ayvakit), with avapritinib mostly used for patients whose GIST harbors an exon 18 mutation.

This is a part of the vision of the future for treating patients with GIST, according to Somaiah, now that patients are responding to later lines of therapy to bolster and find medications that continue to respond to secondary mutations in these patients. These include continuing studies for the use of tyrosine kinase inhibitors (TKIs) in patients with GIST like ripretinib or avapritinib. Other TKIs that could potentially be a larger part of the future of the treatment landscape include sorafenib (Nexavar), nilotinib (Tasigna), dasatinib (Sprycel), and azopanib (Votrient).

Transcription:

0:08 | As you know, [this was] one of the first tumor types where precision oncology made a huge impact with the approval of Gleevec way back in 2002. So since then, what we have 3 drug approvals, and in the last 2 years we have 2 additional drugs approved by looking at more targeted drugs that target the mutations, which we see in KIT or PDGFRA, more effectively.

0:34 | We have been able to get patients to respond even in the later lines of therapy. And what's interesting is what is in the future there at least 5 new drugs in the space that are better and stronger inhibitors of the mutations and secondary mutations we see in GIST. That is likely to make a significant impact in the GIST treatment landscape in the coming years.