2022
DOI: 10.1007/s10120-021-01274-6
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Broad spectrum of regorafenib activity on mutant KIT and absence of clonal selection in gastrointestinal stromal tumor (GIST): correlative analysis from the GRID trial

Abstract: Background In the phase 3 GRID trial, regorafenib improved progression-free survival (PFS) independent of KIT mutations in exons 9 and 11. In this retrospective, exploratory analysis of the GRID trial, we investigated whether a more comprehensive KIT mutation analysis could identify mutations that impact treatment outcome with regorafenib and a regorafenib-induced mutation pattern. Methods Archived tumor samples, collected at any time prior to enrollment i… Show more

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Cited by 4 publications
(3 citation statements)
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“…This has led to the approval of other TK inhibitors, such as sunitinib and regorafenib, with activity against secondary c- kit mutations [ 169 ]. Among these, there are agents such as sunitinib, which elicits longer progression-free survival and overall survival in patients that harbor exon 13 or 14 secondary c- kit mutations compared to those with exon 17 or 18 secondary c- kit mutations [ 167 , 168 ], and regorafenib, which has equal efficacy in tumors with secondary exon 13/14 or exon 17/18 mutations, or combinations thereof [ 170 ]. Ripretinib, a novel type II switch control kinase inhibitor, is a broad-spectrum inhibitor of secondary drug resistance mutations, including activation loop mutations targeted by type I inhibitors [ 171 ].…”
Section: Targeted Therapy Of C-kit-positive Tumorsmentioning
confidence: 99%
“…This has led to the approval of other TK inhibitors, such as sunitinib and regorafenib, with activity against secondary c- kit mutations [ 169 ]. Among these, there are agents such as sunitinib, which elicits longer progression-free survival and overall survival in patients that harbor exon 13 or 14 secondary c- kit mutations compared to those with exon 17 or 18 secondary c- kit mutations [ 167 , 168 ], and regorafenib, which has equal efficacy in tumors with secondary exon 13/14 or exon 17/18 mutations, or combinations thereof [ 170 ]. Ripretinib, a novel type II switch control kinase inhibitor, is a broad-spectrum inhibitor of secondary drug resistance mutations, including activation loop mutations targeted by type I inhibitors [ 171 ].…”
Section: Targeted Therapy Of C-kit-positive Tumorsmentioning
confidence: 99%
“… 102 , 113 Sunitinib is more effective for patients with exon 13/14 secondary c-kit mutations compared to those with exon 17/18 secondary c-kit mutations, 108 , 111 while regorafenib is an effective choice for patients whose tumors harbor secondary exon 13/14 or exon 17/18 mutations. 114 …”
Section: Gastrointestinal Stromal Tumors (Gists)mentioning
confidence: 99%
“…102,113 Sunitinib is more effective for patients with exon 13/14 secondary c-kit mutations compared to those with exon 17/18 secondary c-kit mutations, 108,111 while regorafenib is an effective choice for patients whose tumors harbor secondary exon 13/14 or exon 17/18 mutations. 114 Another TKI that was approved by the US FDA in 2020, based on the positive results obtained from the INVICTUS trial, is ripretinib. It was recommended for advanced or metastatic GIST patients who were resistant to three or more kinase inhibitors including imatinib.…”
Section: Dovepressmentioning
confidence: 99%