• Ana Oaknin, Claire F Friedman, Lynda D Roman, Anishka D'Souza, Irene Brana, François-Clement Bidard, Jonathan Goldman, Edwin A Alvarez, Valentina Boni, Adam C ElNaggar, Rodolfo Passalacqua, Khanh T M Do, Alessandro D Santin, Kiana Keyvanjah, Feng Xu, Lisa D Eli, Alshad S Lalani, Richard P Bryce, David M Hyman, Funda Meric-Bernstam, David B Solit, and Bradley J Monk.
• Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
• Gynecol. Oncol. 2020 Oct 1; 159 (1): 150-156.

ObjectiveSomatic 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.MethodsPatients 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.ResultsSixteen 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.ConclusionsNeratinib 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.Trial Registration NumberNCT01953926 (ClinicalTrials.gov), 2013-002872-42 (EudraCT).Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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