Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 ‘CaboGIST’

Schöffski, Patrick; Mir, Olivier; Kasper, Bernd; Pápai, Zsuzsanna; Blay, Jean‐Yves; Italiano, Antoîne; Benson, Charlotte; Kopečková, Kateřina; Ali, Nasim; Dileo, Palma; Lecesne, A.; Menge, Franka; Cousin, Sophie; Wardelmann, Eva; Woźniak, Agnieszka; Marréaud, Sandrine; Litière, Saskia; Zaffaroni, Facundo; Nzokirantevye, Axelle; Bempt, Isabelle Vanden; Gelderblom, Hans

doi:10.1016/j.ejca.2020.04.021

Cited by 50 publications

(42 citation statements)

References 25 publications

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“…The tolerability of cabozantinib in the CaboGIST study reported by Schöffski et al [55] was consistent with that observed in previous clinical trials in other indications. AEs were similar to those reported for other TKIs and were generally managed with dose modification and symptomatic treatment.…”

Section: Cabozantinibsupporting

confidence: 89%

“…The most common treatment-related AEs, in more than 25% of patients, were diarrhea, fatigue, hypertension, stomatitis, weight loss, and HFS. Grade 3 or higher diarrhea was reported in 26% of patients, and HFS was reported in 8% of patients [55]. No unexpected AEs were observed.…”

Section: Cabozantinibmentioning

confidence: 87%

“…The mutational analysis was conducted in archival tissue samples from 37 patients. The most frequently found mutations were KIT mutations (83.3%) [55].…”

Section: Cabozantinibmentioning

confidence: 99%

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Treatment of Metastatic Gastrointestinal Stromal Tumors (GIST): A Focus on Older Patients

et al. 2021

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Gastrointestinal stromal tumors (GIST) originating in the Cajal cells are the most common mesenchymal neoplasms of the gastrointestinal tract. The median age of patients with this diagnosis is 65 years, and over 20% of cases affect people over the age of 70 years. The effectiveness and tolerability of systemic treatment with tyrosine kinase inhibitors in older patients with GIST seem to be similar to that in younger patients, but some studies have shown that treatment of older patients is suboptimal. Disability, frailty, comorbidities, and concomitant medications may influence treatment decisions, and toxicities also more often lead to treatment discontinuation. The known safety profile and oral administration route of the tyrosine kinase inhibitors used in GIST may allow maximization of treatment and the best efficacy, especially in older patients. This review summarizes the efficacy data for the systemic treatment of GIST, including data for older patients and from real-world experiences, if available and significant. The reported safety data and general rules for toxicity management, including appropriate patient selection and the need for careful monitoring during treatment, are also discussed.

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Section: Cabozantinibsupporting

confidence: 89%

Section: Cabozantinibmentioning

confidence: 87%

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Treatment of Metastatic Gastrointestinal Stromal Tumors (GIST): A Focus on Older Patients

et al. 2021

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“…These studies were small phase II trials. The drugs investigated include sorafenib, pazopanib, cabozantinib, nilotinib, dasatinib, masitinib, linsitinib, dovitinib, vatalanib and ponatinib [34,41,[54][55][56][57][58][59][60][61][62][63]. The response and survival outcomes reported in these studies are conveyed in Table 2.…”

Section: Alternative Tkis Previously Investigated In Patients With Advanced Gistmentioning

confidence: 99%

The management of metastatic GIST: current standard and investigational therapeutics

2021

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Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The majority of GISTs harbor gain of function mutations in either KIT or PDGFRα. Determination of the GIST molecular subtype upon diagnosis is important because this information informs therapeutic decisions in both the adjuvant and metastatic setting. The management of GIST was revolutionized by the introduction of imatinib, a KIT inhibitor, which has become the standard first line treatment for metastatic GIST. However, despite a clinical benefit rate of 80%, the majority of patients with GIST experience disease progression after 2–3 years of imatinib therapy. Second and third line options include sunitinib and regorafenib, respectively, and yield low response rates and limited clinical benefit. There have been recent FDA approvals for GIST including ripretinib in the fourth-line setting and avapritinib for PDGFRA exon 18-mutant GIST. This article aims to review the optimal treatment approach for the management of patients with advanced GIST. It examines the standard treatment options available but also explores the novel treatment approaches in the setting of imatinib refractory GIST.

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“…In patient-derived mouse GIST xenografts, cabozantinib exhibits anti-tumor activity by inhibition of tumor growth proliferation and angiogenesis in imatinib-resistant models [16]. In the EORTC 1317 phase 2 CaboGIST study [30], 50 patients with metastatic GIST, progressive on imatinib and sunitinib were included. The study decision rule to justify further investigation with cabozantinib was defined as, if at least 21 of the first 41 evaluated patients were progression-free at week 12.…”

Section: Cabozantinibmentioning

confidence: 99%

Systemic therapy of advanced/metastatic gastrointestinal stromal tumors: an update on progress beyond imatinib, sunitinib, and regorafenib

Mohammadi

Gelderblom

2020

Expert Opinion on Investigational Drugs

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Introduction: Discovery of oncogenic mutations in the KIT and PDGFRA tyrosine kinase receptor was a crucial step for the development of tyrosine kinase inhibitors (TKIs). Since then, GIST became a model for the development of molecular-targeted therapy, which led to dramatically improved median overall survival of advanced GIST. Still, further progress is needed after third-line or for TKI resistant mutations. Areas covered: In this review, after a brief introduction on imatinib, sunitinib, and regorafenib, an overview of TKIs that was evaluated beyond these drugs is provided, with a main focus on the novel approved TKIs. Expert opinion: Combination therapies have thus far not fulfilled their promise in GIST, nor did immunotherapy. Increased understanding of GIST and advances in the development of moleculartargeted drugs led to the introduction of ripretinib and avapritinib. Furthermore, NTRK inhibitors became available for ultrarare NTRK fusions. Solutions for NF1 and BRAF mutated and SDH-deficient GIST are still to be awaited. This all underlines the need for adequate molecular profiling of high-risk GISTs before treatment is started. Possibly by using circulating tumor DNA in the future, targeting resistance mutations with specific drugs along the course of the disease would be easier, avoiding multiple tumor biopsies.

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Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 ‘CaboGIST’

Cited by 50 publications

References 25 publications

Treatment of Metastatic Gastrointestinal Stromal Tumors (GIST): A Focus on Older Patients

Treatment of Metastatic Gastrointestinal Stromal Tumors (GIST): A Focus on Older Patients

The management of metastatic GIST: current standard and investigational therapeutics

Systemic therapy of advanced/metastatic gastrointestinal stromal tumors: an update on progress beyond imatinib, sunitinib, and regorafenib

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