Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial.
Gynecol Oncol
; 159(1): 150-156, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-32723675
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. TRIAL REGISTRATION NUMBER NCT01953926 (ClinicalTrials.gov), 2013-002872-42 (EudraCT).Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinolines
/
Uterine Cervical Neoplasms
/
Receptor, ErbB-2
/
Protein Kinase Inhibitors
/
Neoplasm Recurrence, Local
Type of study:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Gynecol Oncol
Year:
2020
Document type:
Article
Affiliation country:
Spain