Patients with SDH-deficient gastrointestinal stromal tumors (GISTs) should refer to specialized centers so data and reliable clinical evidence about the efficacy of tyrosine kinase inhibitors can be collected when treating them.

This is the conclusion of a review of the current evidence on the treatment of SDH-deficient GISTs that was published in the journal Therapeutic Advances in Medical Oncology.

SDH-deficient GIST is a rare form of the disease, which mostly occurs in younger patients; treatment of it with tyrosine kinase inhibitors remains controversial.

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“Thus, there is an urgent need to uncover the disease mechanisms, treatment patterns, and responses to systemic therapy among these patients,” wrote Margherita Nannini, MD, and the co-authors of the study.

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Only very limited data is available on the effectiveness of tyrosine kinase inhibitors in treating SDH-deficient GISTs, mainly due to the fact that this molecular subtype of the disease is so rare and also because most SDH-deficient GISTs were described as KIT/PDGFRA wild-type GISTs in the past.

Here, the authors report data about the effectiveness of 6 tyrosine kinase inhibitors in treating SDH-deficient GISTs. These are sunitinib, regorafenib, pazopanib, nilotinib, linsitinib, and vandetanib.

According to the review, 2 studies suggested the efficacy of sunitinib in controlling the disease in patients with SDH-deficient GISTs. In another study, regorafenib was shown to be effective in patients with SDH-deficient GISTs.

The results of a phase 2 clinical trial have shown that pazopanib could confer prolonged disease control after 17 cycles of treatment in patients with GISTs but only 1 patient had SDH-deficient GISTs.

The effectiveness of nilotinib in patients with SDH-deficient GISTs remains controversial, with only 2 young adult patients achieving a remarkable and durable response to nilotinib treatment.

Results of a phase 2 study suggested a potential benefit of linsitinib in patients with SDH-deficient GISTs while the results of another phase 2 trial suggested that vandetanib is not active in this patient population.

KIT and PDGFRA mutations are central events in the pathogenesis of GISTs. However, about 5% to 10% of GISTs do not have a mutation in these genes and about a half of those are deficient in SDH.


Nannini M, Rizzo A, Indio V, Schipani A, Astolfi A, Pantaleo MA. Targeted therapy in SDH-deficient GIST. Ther Adv Med Oncol. 2021;28;13:17588359211023278. doi:10.1177/17588359211023278