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Ref Type Journal Article
PMID (32723675)
Authors Oaknin A, Friedman CF, Roman LD, D'Souza A, Brana I, Clement-Bidard F, Goldman J, Alvarez EA, Boni V, ElNaggar AC, Passalacqua R, Do KTM, Santin AD, Keyvanjah K, Xu F, Eli LD, Lalani AS, Bryce RP, Hyman DM, Meric-Bernstam F, Solit DB, Monk BJ
Title Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial.
Journal Gynecologic oncology
Vol
Issue
Date 2020 Jul 25
URL
Abstract Text 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.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.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.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.NCT01953926 (ClinicalTrials.gov), 2013-002872-42 (EudraCT).

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 S310F ERBB2 V842I cervical cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a Phase II trial (SUMMIT), a heavily pretreated cervical cancer patient co-harboring ERBB2 (HER2) S310F and ERBB2 (HER2) V842I demonstrated a partial response when treated with Nerlynx (neratinib) (PMID: 32723675; NCT01953926). 32723675
ERBB2 R678Q cervical cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a Phase II trial (SUMMIT), a heavily pretreated cervical cancer patient harboring ERBB2 (HER2) R678Q demonstrated stable disease when treated with Nerlynx (neratinib) (PMID: 32723675; NCT01953926). 32723675
ERBB2 act mut cervical cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), heavily pretreated cervical cancer patients harboring an ERBB2 (HER2) mutation demonstrated an objective response rate of 25% (4/16), including 1 complete response and 3 partial responses, a median progression-free survival of 7.0 months, a median overall survival of 16.8 months, and a clinical benefit rate of 43.8% (7/16) when treated with Nerlynx (neratinib) (PMID: 32723675; NCT01953926). 32723675
ERBB2 G776V cervical cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a Phase II trial (SUMMIT), a heavily pretreated cervical cancer patient harboring ERBB2 (HER2) G776V demonstrated stable disease when treated with Nerlynx (neratinib) (PMID: 32723675; NCT01953926). 32723675