Revolutions in treatment options in gastrointestinal stromal tumours (GISTs): the latest updates

Sheima Farag, Myles J Smith, Nicos Fotiadis, Anastasia Constantinidou, Robin L Jones, Sheima Farag, Myles J Smith, Nicos Fotiadis, Anastasia Constantinidou, Robin L Jones

Abstract

The treatment of advanced GIST is rapidly evolving with the development of novel molecular compounds such as avapritinib and ripretinib, but also promising results have been achieved with cabozantinib in a phase II trial. The availability of over five lines of treatment for patients with advanced GIST is likely to completely shift the current second-line and third-line treatment options, and will also potentially enable a personalised approach to treatment. Imatinib will most likely remain as the first-line treatment of choice for the vast majority of GIST patients. However, for GIST patients with tumours harbouring a D842V mutation in PDGFRA exon 18, avapritinib has shown efficacy and will become first-line therapy for this molecular subgroup. For second- and third-line treatment, results are awaited of a number of clinical trials. However, second-line and further treatment could potentially be tailored depending on secondary mutations found in imatinib-resistant GISTs. As secondary resistance to TKIs remains the biggest challenge in the treatment of GIST and despite negative results with alternating regimens in phase II, combination treatments should be further evaluated to tackle this issue. Moreover, the favourable safety profiles observed with avapritinib and ripretinib suggest that combination treatments are feasible, for instance, combining two TKIs or a TKI with drugs targeting downstream signalling pathways, such as PI3K inhibitors or MEK inhibitors. Finally, in line with further personalisation of treatment in GIST, a multidisciplinary approach is essential, and local treatment options, such as RFA, resection in case of unifocal progression, and radiotherapy, should be considered.

Keywords: Avapritinib; GIST; Gastrointestinal stromal tumour; Ripretinib; TKI; Tyrosine kinase inhibitors.

Conflict of interest statement

Drs. Farag, Fotiadis, and Constantinidou do not have any conflicts of interest to disclose. Dr. Smith, however, has received compensation from MSFS for service as a consultant and has received compensation from Amgen for participating on an advisory board. Additionally, Dr. Jones has received compensation from Adaptimmune, Blueprint Medicines, Clinigen, Eisai, Epizyme, Daiichi, Deciphera, Immune Design, Lilly, Pharma Mar, and UpToDate for service as a consultant.

Figures

Fig. 1
Fig. 1
Suggested potential treatment paradigm based on personalised approach following the latest advances in the field. *Beyond third-line patients’ performance status and comorbidities should be considered.

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