TY - JOUR
T1 - Neratinib in patients with HER2-mutant, metastatic cervical cancer
T2 - Findings from the phase 2 SUMMIT basket trial
AU - Oaknin, Ana
AU - Friedman, Claire F.
AU - Roman, Lynda D.
AU - D'Souza, Anishka
AU - Brana, Irene
AU - Bidard, François Clement
AU - Goldman, Jonathan
AU - Alvarez, Edwin A.
AU - Boni, Valentina
AU - ElNaggar, Adam C.
AU - Passalacqua, Rodolfo
AU - Do, Khanh T.M.
AU - Santin, Alessandro D.
AU - Keyvanjah, Kiana
AU - Xu, Feng
AU - Eli, Lisa D.
AU - Lalani, Alshad S.
AU - Bryce, Richard P.
AU - Hyman, David M.
AU - Meric-Bernstam, Funda
AU - Solit, David B.
AU - Monk, Bradley J.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/10
Y1 - 2020/10
N2 - 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).
AB - 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).
KW - Cervical cancer
KW - Clinical trial
KW - HER2 mutant
KW - Neratinib
KW - Tyrosine kinase inhibitor
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U2 - 10.1016/j.ygyno.2020.07.025
DO - 10.1016/j.ygyno.2020.07.025
M3 - Article
C2 - 32723675
AN - SCOPUS:85088805757
SN - 0090-8258
VL - 159
SP - 150
EP - 156
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 1
ER -