RT Journal Article
T1 Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib.
A1 Serrano, César
A1 García-Del-Muro, Xavier
A1 Valverde, Claudia
A1 Sebio, Ana
A1 Durán, José
A1 Manzano, Aránzazu
A1 Pajares, Isabel
A1 Hindi, Nadia
A1 Landolfi, Stefania
A1 Jiménez, Laura
A1 Rubió-Casadevall, Jordi
A1 Estival, Anna
A1 Lavernia, Javier
A1 Safont, María José
A1 Pericay, Carles
A1 Díaz-Beveridge, Roberto
A1 Martínez-Marín, Virginia
A1 Vicente-Baz, David
A1 Vivancos, Ana
A1 Hernández-Losa, Javier
A1 Arribas, Joaquín
A1 Carles, Joan
K1 Gastrointestinal stromal tumor
K1 Imatinib mesylate
K1 Long‐term
K1 c‐KIT
AB Oncogenic KIT/PDGFRA signaling inhibition with imatinib achieves disease control in most patients with advanced/metastatic gastrointestinal stromal tumor (GIST), but resistance eventually develops after 20-24 months. Notably, a small subset of these patients obtain durable benefit from imatinib therapy. We analyzed clinical, pathological, and molecular characteristics and long-term outcomes in patients with metastatic GIST treated with continuous daily dosing of frontline imatinib in a cohort of patients benefiting for ≥5 years. A control group was obtained from the national Spanish Group for Sarcoma Research database and used as comparator. Sixty-four imatinib long-term responders (LTRs) and 70 control cases were identified. Compared with controls, LTRs at baseline had better performance status (PS) 0-1 (100% vs. 81%), lower mitotic count (median, 8 vs. 15), and tumor burden (number of metastases, 3 vs. 7). KIT exon 11 was the only region found mutated in LTRs. LTRs achieved 34% complete responses and a median progression-free survival of 11 years, compared with 4% and 2 years, respectively, in the control cohort. Prognostic factors that independently predicted long-term benefit with imatinib were PS, number of metastases prior to imatinib, and response to imatinib. Fifteen LTR patients developed new side effects attributable to imatinib after ≥5 years of continuous treatment. No resistance mutations were found in metastatic samples from three patients progressing on imatinib. GISTs in LTRs are a distinctive entity with less aggressive behavior and marked sensitivity to KIT inhibition. Patients reaching 5 or more years on imatinib have a higher chance of remaining progression free over time. This work demonstrates that clinical and inherent tumor characteristics define a subset of patients with gastrointestinal stromal tumor (GIST) with increased likelihood to achieve durable response to first-line imatinib therapy. Patients reaching ≥5 years on imatinib have a greater chance of remaining progression free over time, although the disease is unlikely to be cured. Imatinib is well tolerated for >5 years, and emergent toxicities are overall manageable. Resistance to imatinib emerging in patients with GISTs after long-term imatinib treatment does not involve polyclonal expansion of KIT secondary mutations.
YR 2018
FD 2018-08-20
LK http://hdl.handle.net/10668/12858
UL http://hdl.handle.net/10668/12858
LA en
DS RISalud
RD Apr 7, 2025