1. Neratinib in patients with HER2 -mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial
- Author
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Khanh T. Do, Claire F. Friedman, François-Clément Bidard, Richard Bryce, Anishka D'souza, Bradley J. Monk, Adam C. ElNaggar, Lynda D. Roman, Feng Xu, Irene Brana, Kiana Keyvanjah, Edwin A. Alvarez, Funda Meric-Bernstam, Rodolfo Passalacqua, David M. Hyman, Valentina Boni, David B. Solit, Ana Oaknin, Alessandro D. Santin, Jonathan H. Goldman, Lisa D. Eli, Alshad S. Lalani, Institut Català de la Salut, [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, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
0301 basic medicine ,Oncology ,Receptor, ErbB-2 ,Neratinib ,Administration, Oral ,Uterine Cervical Neoplasms ,Tyrosine kinase inhibitor ,Kaplan-Meier Estimate ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Severity of Illness Index ,Tyrosine-kinase inhibitor ,ErbB-2 ,0302 clinical medicine ,Clinical endpoint ,6.2 Cellular and gene therapies ,Cancer ,Cervical cancer ,Obstetrics and Gynecology ,Nausea ,Middle Aged ,Progression-Free Survival ,Clinical trial ,Diarrhea ,Local ,6.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Administration ,Quinolines ,Female ,medicine.symptom ,neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias del cuello uterino [ENFERMEDADES] ,Receptor ,medicine.drug ,Oral ,Adult ,medicine.medical_specialty ,medicine.drug_class ,Clinical Trials and Supportive Activities ,Oncology and Carcinogenesis ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasms [DISEASES] ,Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [CHEMICALS AND DRUGS] ,Article ,Paediatrics and Reproductive Medicine ,Coll uterí - Càncer - Tractament ,03 medical and health sciences ,Clinical Research ,Internal medicine ,medicine ,Humans ,Oncology & Carcinogenesis ,Adverse effect ,Protein Kinase Inhibitors ,Response Evaluation Criteria in Solid Tumors ,business.industry ,acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas [COMPUESTOS QUÍMICOS Y DROGAS] ,medicine.disease ,Proteïnes quinases - Inhibidors ,Neoplasm Recurrence ,030104 developmental biology ,Mutation ,Neoplasm Recurrence, Local ,business ,HER2 mutant - Abstract
Càncer de coll uterí; Assaig clínic; Mutant HER2 Cáncer de cuello uterino; Ensayo clínico; Mutante HER2 Cervical cancer; Clinical trial; HER2 mutant 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. This work was supported by Puma Biotechnology Inc . 10880 Wilshire Blvd, Suite 2150, Los Angeles, CA 90024, USA.
- Published
- 2020