4 results on '"Valverde, Claudia"'
Search Results
2. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward.
- Author
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Lostes-Bardaji, M. Julia, García-Illescas, David, Valverde, Claudia, and Serrano, César
- Abstract
Gastrointestinal stromal tumor (GIST) represents a paradigm for clinically effective targeted inhibition of oncogenic driver mutations in cancer. Five drugs are currently positioned as the standard of care for the treatment of advanced or metastatic GIST patients. This is the result of continuous, deep understanding of KIT and PDGFRA GIST oncogenic drivers as well as the resistance mechanisms associated to tumor progression. However, the complexity of GIST molecular heterogeneity is an evolving field, and critical questions remain open. Specifically, the clinical benefit of approved and/or investigated targeted agents is strikingly modest at advanced stages of the disease when compared with the activity of first-line imatinib. Ripretinib is a novel switch-pocket inhibitor with broad activity against KIT and PDGFRA oncoproteins and has recently demonstrated antitumoral activity across phase I to phase III clinical trials. Therefore, ripretinib has emerged as a new standard of care for advanced, multi-resistant GIST patients. Based on this data, the Food and Drug Administration has granted in 2020 the approval of ripretinib for GIST patients after progression to imatinib, sunitinib and regorafenib. This, in turn, constitutes a major breakthrough in sarcoma drug development, as there have not been new treatment approvals in GIST for nearly a decade. Herein, we provide a critical review on the preclinical and clinical development of ripretinib in GIST. Furthermore, we seek to assess the biological and clinical impact of this new standard of care on the course of the disease, aiming to provide an insight on future treatments strategies for the next coming years. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
3. Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib.
- Author
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Serrano, César, García‐del‐Muro, Xavier, Valverde, Claudia, Sebio, Ana, Durán, José, Manzano, Aránzazu, Pajares, Isabel, Hindi, Nadia, Landolfi, Stefania, Jiménez, Laura, Rubió‐Casadevall, Jordi, Estival, Anna, Lavernia, Javier, Safont, María José, Pericay, Carles, Díaz‐Beveridge, Roberto, Martínez‐Marín, Virginia, Vicente‐Baz, David, Vivancos, Ana, and Hernández‐Losa, Javier
- Subjects
GASTROINTESTINAL tumors ,CYTOGENETICS ,SARCOMA ,DRUG side effects ,SYMPTOMS ,TREATMENT effectiveness ,TREATMENT duration ,CANCER patients ,METASTASIS ,CONNECTIVE tissue tumors ,LONGITUDINAL method ,IMATINIB ,GENETIC mutation ,DISEASE progression - Abstract
Background: 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. Methods: 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. Results: 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. Conclusion: 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. Implications for Practice: 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. This article identifies distinctive clinicopathological and molecular features in long‐term responders to imatinib treatment compared with patients with gastrointestinal stromal tumors reaching the usual median progression‐free survival. Clinical insights from this subgroup collected during the long‐term follow‐up are also provided. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
4. GEIS 2013 guidelines for gastrointestinal sarcomas (GIST).
- Author
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Poveda, Andrés, Muro, Xavier, López-Guerrero, Jose, Martínez, Virginia, Romero, Ignacio, Valverde, Claudia, Cubedo, Ricardo, and Martín-Broto, Javier
- Subjects
SARCOMA ,GASTROINTESTINAL stromal tumors ,SOFT tissue tumors ,GENETIC mutation ,DRUG development ,PLATELET-derived growth factor receptors ,DIAGNOSIS - Abstract
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. Correct diagnosis with thorough use of pathologic and molecular tools of GIST mutations has been of the foremost importance. GIST are usually (95 %) KIT positive and harbor frequent KIT or platelet-derived growth factor receptor α-activating mutations. This deep molecular understanding has allowed the correct classification into risk groups with implications regarding prognosis, essential use in the development of targeted therapies and even response prediction to this drugs. Treatment has been evolving and an update to include lessons learned from recent trials in advanced disease as well as controversies in the adjuvant setting that are changing daily practice, is reviewed here. An effort from the Spanish Group for Sarcoma Research with investigators from the group has been undertaken to launch this third version of the GIST guidelines and provide a practical means for the different disciplines that treat this complex disease. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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