Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial Journal Article


Authors: Oaknin, A.; Friedman, C. F.; Roman, L. D.; D'Souza, A.; Brana, I.; Bidard, F. C.; Goldman, J.; Alvarez, E. A.; Boni, V.; ElNaggar, A. C.; Passalacqua, R.; Do, K. T. M.; Santin, A. D.; Keyvanjah, K.; Xu, F.; Eli, L. D.; Lalani, A. S.; Bryce, R. P.; Hyman, D. M.; Meric-Bernstam, F.; Solit, D. B.; Monk, B. J.
Article Title: Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial
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). © 2020 The Authors
Keywords: adult; cancer chemotherapy; clinical article; treatment response; cancer surgery; overall survival; somatic mutation; clinical trial; constipation; cancer recurrence; bevacizumab; cisplatin; advanced cancer; diarrhea; drug efficacy; drug safety; monotherapy; multimodality cancer therapy; recommended drug dose; treatment duration; paclitaxel; cancer radiotherapy; topotecan; cancer staging; nuclear magnetic resonance imaging; carboplatin; metastasis; progression free survival; computer assisted tomography; phase 2 clinical trial; nausea; vomiting; cancer pain; abdominal pain; asthenia; backache; dyspnea; insomnia; maculopapular rash; malaise; uterine cervix cancer; muscle weakness; peripheral edema; xerostomia; anxiety disorder; cancer fatigue; loperamide; dermatitis; headache; tyrosine kinase inhibitor; cystitis; dyspepsia; muscle spasm; dry skin; race difference; epistaxis; disease exacerbation; cervical cancer; neratinib; decreased appetite; cancer prognosis; high throughput sequencing; human; female; priority journal; article; pembrolizumab; patient history of radiotherapy; her2 mutant
Journal Title: Gynecologic Oncology
Volume: 159
Issue: 1
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2020-10-01
Start Page: 150
End Page: 156
Language: English
DOI: 10.1016/j.ygyno.2020.07.025
PUBMED: 32723675
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 2 November 2020 -- Source: Scopus
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MSK Authors
  1. David Solit
    629 Solit
  2. David Hyman
    345 Hyman