What Supports the Use of Bezuclastinib/Sunitinib in Second-line GIST?


Antonio Ucar, MD, explains the rationale behind the phase 3 Peak study of bezuclastinib plus sunitinib in patients with gastrointestinal stromal tumors being treated in the second-line setting.

Antonio Ucar, MD, an oncologist/hematologist at Miami Cancer Institute of Baptist Health South Florida, explains the rationale behind the phase 3 Peak study, which investigates second-line treatment with bezuclastinib plus sunitinib (Sutent) in patients with gastrointestinal stromal tumors.

Ucar says in the full interview with Targeted Oncology™ that imatinib (Gleevec) is the standard frontline treatment, but most patients relapse, and there is a need for additional treatment options in this setting. Phase 1a findings from the Peak study hint that bezuclastinib plus sunitinib is a potential option.


0:08 | Sunitinib has activity against primary KIT mutations. It also has activity against some of the secondary KIT mutations. To explain a little bit about the mutations, there are 2 major mutations that we identify in tumors in GIST. When it's a KIT mutation, which is the most common one seen in about 70% to 80% of the cases, there is a PDGFRA mutation in 5% to 10% of patients. Then, there's a 10% to 15% chance where both the KIT and the PDGFRA mutation are wild type. So, there's no mutation basically.

1:07 | Sunitinib, as I mentioned, has activity against the primary KIT mutations and secondary KIT mutations. But there are other mutations in particular KIT exon 17 and 18 mutations that are resistant to sunitinib, and this mutation is of very poor prognosis because it renders the tumor resistant. The tumor continues to grow despite a multitude of treatments. With the addition of this new medication, bezuclastinib, it targets that KIT exon 17/18 mutation. The idea is to cover as many mutation options as possible. There is no escape to the activity of the disease. Like in many other diseases, including cancer, we use a multitude of drugs that work by different mechanisms of actions that have different targets, to try to optimize the control and the response of the tumor.

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