dc.contributor
Institut Català de la Salut
dc.contributor
[Oaknin A, Brana I] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Friedman CF] Memorial Sloan Kettering Cancer Center, New York, NY, USA. [Roman LD, D'Souza A] USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA. [Bidard FC] Institut Curie, St Cloud, France
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Oaknin Benzaquen, Ana Mazaltob
dc.contributor.author
Friedman, Claire F.
dc.contributor.author
Roman, Lynda D.
dc.contributor.author
D'Souza, Anishka
dc.contributor.author
Braña Garcia, Irene
dc.contributor.author
Bidard, François-Clement
dc.date.accessioned
2023-11-08T10:19:00Z
dc.date.available
2023-11-08T10:19:00Z
dc.date.issued
2021-09-21T10:47:42Z
dc.date.issued
2021-09-21T10:47:42Z
dc.identifier
Oaknin A, Friedman CF, Roman LD, D'Souza A, Brana I, Bidard FC, et al. Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial. Gynecol Oncol. 2020 Oct;159:150–6.
dc.identifier
https://hdl.handle.net/11351/6338
dc.identifier
10.1016/j.ygyno.2020.07.025
dc.identifier
000576604900023
dc.identifier.uri
https://hdl.handle.net/11351/6338
dc.description.abstract
Càncer de coll uterí; Assaig clínic; Mutant HER2
dc.description.abstract
Cáncer de cuello uterino; Ensayo clínico; Mutante HER2
dc.description.abstract
Cervical cancer; Clinical trial; HER2 mutant
dc.description.abstract
Objective: Somatic HER2 mutations occur in ~5% of cervical cancers and are considered oncogenic and associated with poor prognosis. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, is active in multiple HER2-mutant cancers. SUMMIT is a phase II basket trial investigating the efficacy and safety of neratinib in solid tumors.
Methods: Patients with HER2-mutant, persistent, metastatic/recurrent cervical cancer with disease progression after platinum-based treatment for advanced/recurrent disease received oral neratinib 240 mg/day with mandatory loperamide prophylaxis during cycle 1. The primary endpoint was confirmed objective response rate (ORR). Secondary endpoints included: response duration (DOR); clinical benefit rate (CBR); progression-free survival (PFS); overall survival (OS); safety.
Results: Sixteen eligible patients were enrolled; 10 (62.5%) had endocervical adenocarcinoma. The most common HER2 mutation was S310F (63% of patients). Three of 12 RECIST-measurable patients had confirmed partial responses (ORR 25%; 95%CI 5.5-57.2%); 3 had stable disease ≥16 weeks (CBR 50%; 95%CI 21.1-78.9%). DOR for responders were 5.6, 5.9, and 12.3 months. Median PFS was 7.0 months (95%CI 0.7-18.3 months); median OS was 16.8 months (95%CI 4.1-NE months). Diarrhea (75%), nausea (44%), and decreased appetite (38%) were the most common adverse events. One patient (6%) reported grade 3 diarrhea. There were no grade 4 events, and no diarrhea-related treatment discontinuations.
Conclusions: Neratinib monotherapy showed evidence of activity in heavily pretreated patients with HER2-mutant cervical cancer, with no new safety signals. Given the few effective options for cervical cancer after platinum-based therapy failure, neratinib warrants further investigation in this molecularly defined patient population.
dc.description.abstract
This work was supported by Puma Biotechnology Inc . 10880 Wilshire Blvd, Suite 2150, Los Angeles, CA 90024, USA.
dc.format
application/pdf
dc.relation
Gynecologic Oncology;159
dc.relation
https://doi.org/10.1016/j.ygyno.2020.07.025
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Coll uterí - Càncer - Tractament
dc.subject
Proteïnes quinases - Inhibidors
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasms
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias del cuello uterino
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Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas
dc.title
Neratinib in patients with HER2 -mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
