Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib : a Phase 1b, multicentre study
BACKGROUND: The majority of patients with advanced gastrointestinal stromal tumours (GISTs) develop resistance to imatinib and sunitinib, the standard of care for these patients. This study evaluated the combination of buparlisib, an oral phosphoinositide 3-kinase (PI3K) inhibitor, with imatinib in patients with advanced GIST, who have failed prior therapy with imatinib and sunitinib.
METHODS: This Phase 1b, multicentre, open-label study aimed to determine the maximum tolerated dose (MTD) and/or a recommended Phase 2 dose of buparlisib in combination with 400 mg of imatinib through a dose-escalation part and a dose-expansion part, and also evaluated the clinical profile of the combination.
RESULTS: Sixty patients were enrolled, including 25 in the dose-escalation part and 35 in the dose-expansion part. In the combination, MTD of buparlisib was established as 80 mg. No partial or complete responses were observed. The estimated median progression-free survival was 3.5 months in the expansion phase. Overall, 98.3% of patients had treatment-related adverse events (AEs), including 45% with grade 3 or 4 AEs.
CONCLUSIONS: Buparlisib in combination with imatinib provided no additional benefit compared with currently available therapies. Due to the lack of objective responses, further development of this combination was not pursued for third-line/fourth-line advanced/metastatic GIST.
TRIAL REGISTRATION NUMBER: NCT01468688.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:122 |
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| Enthalten in: |
British journal of cancer - 122(2020), 8 vom: 01. Apr., Seite 1158-1165 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gelderblom, Hans [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.12.2020 Date Revised 10.03.2021 published: Print-Electronic ClinicalTrials.gov: NCT01468688 Citation Status MEDLINE |
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| doi: |
10.1038/s41416-020-0769-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM307360563 |
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| 100 | 1 | |a Gelderblom, Hans |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib |b a Phase 1b, multicentre study |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 30.12.2020 | ||
| 500 | |a Date Revised 10.03.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT01468688 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: The majority of patients with advanced gastrointestinal stromal tumours (GISTs) develop resistance to imatinib and sunitinib, the standard of care for these patients. This study evaluated the combination of buparlisib, an oral phosphoinositide 3-kinase (PI3K) inhibitor, with imatinib in patients with advanced GIST, who have failed prior therapy with imatinib and sunitinib | ||
| 520 | |a METHODS: This Phase 1b, multicentre, open-label study aimed to determine the maximum tolerated dose (MTD) and/or a recommended Phase 2 dose of buparlisib in combination with 400 mg of imatinib through a dose-escalation part and a dose-expansion part, and also evaluated the clinical profile of the combination | ||
| 520 | |a RESULTS: Sixty patients were enrolled, including 25 in the dose-escalation part and 35 in the dose-expansion part. In the combination, MTD of buparlisib was established as 80 mg. No partial or complete responses were observed. The estimated median progression-free survival was 3.5 months in the expansion phase. Overall, 98.3% of patients had treatment-related adverse events (AEs), including 45% with grade 3 or 4 AEs | ||
| 520 | |a CONCLUSIONS: Buparlisib in combination with imatinib provided no additional benefit compared with currently available therapies. Due to the lack of objective responses, further development of this combination was not pursued for third-line/fourth-line advanced/metastatic GIST | ||
| 520 | |a TRIAL REGISTRATION NUMBER: NCT01468688 | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Aminopyridines |2 NLM | |
| 650 | 7 | |a Morpholines |2 NLM | |
| 650 | 7 | |a NVP-BKM120 |2 NLM | |
| 650 | 7 | |a Phosphoinositide-3 Kinase Inhibitors |2 NLM | |
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| 650 | 7 | |a V99T50803M |2 NLM | |
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| 700 | 1 | |a George, Suzanne |e verfasserin |4 aut | |
| 700 | 1 | |a Valverde Morales, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Benson, Charlotte |e verfasserin |4 aut | |
| 700 | 1 | |a Jean-Yves Blay |e verfasserin |4 aut | |
| 700 | 1 | |a Renouf, Daniel J |e verfasserin |4 aut | |
| 700 | 1 | |a Doi, Toshihiko |e verfasserin |4 aut | |
| 700 | 1 | |a Le Cesne, Axel |e verfasserin |4 aut | |
| 700 | 1 | |a Leahy, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Hertle, Sabine |e verfasserin |4 aut | |
| 700 | 1 | |a Aimone, Paola |e verfasserin |4 aut | |
| 700 | 1 | |a Brandt, Ulrike |e verfasserin |4 aut | |
| 700 | 1 | |a Schӧffski, Patrick |e verfasserin |4 aut | |
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