Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours

Abstract

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. Surgical treatment is recommended for the majority of localised GIST, while systemic treatment is the cornerstone of management for metastatic or unresectable disease. While a three-year regimen of imatinib is the standard of care in the adjuvant setting, there is no precise recommendation for the duration of neoadjuvant treatment, where imatinib is usually given between 4 and 12 months. Continuous treatment with imatinib at a dose of 400 mg once per day is recommended for most patients with unresectable or metastatic GIST in the first line. An exception is represented by patients with tumours harbouring the imatinib-insensitive PDGFRA D842V mutation who would be better treated with avapritinib. Targeted therapies are also recommended in the presence of NTRK rearrangements and BRAF mutations, although limited data are available. While an increase in the dose of imatinib to 800 mg is an option for the second line, sunitinib is usually considered the standard of care. Similar outcomes were reported for ripretinib in patients with tumours harbouring KIT exon 11 mutation, with significantly fewer side effects. Regorafenib and ripretinib are the standards of care in the third and fourth lines, respectively. The recent development of various systemic treatment options allows for a more personalised approach based on the molecular profile of the GIST, patient characteristics, and the profile of medications’ adverse events. A multidisciplinary approach is paramount since combining systemic treatment with locoregional treatment options and supportive care is vital for long-term survival.

Reply to Chen, A.; Zhang, X. Comment on “Golčić et al. Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours. Cancers 2023, 15, 4081”

“…We appreciate the comment made by Chen et al on our manuscript evaluating the systemic treatment options for gastrointestinal stromal tumours (GIST) [1]. Their comment serves as a reminder of the complexity and issues surrounding the treatment of GIST, and we are thankful to the authors for carefully reading our manuscript.…”

Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment

“…It binds to the ATP pocket at a kinase active site, thus preventing the downstream phosphorylation of target proteins. IMA is the most common first-line cytotoxic agent for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST) in systemic therapy, but CML stem cells are intrinsically resistant to IMA [105,106].…”

Comment on Golčić et al. Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours. Cancers 2023, 15, 4081

“…We carefully read the article written by Golčić et al "Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours" [1]. The authors included the dose escalation of imatinib as an option for the second-line treatment of metastatic or unresectable GISTs.…”