医学
内科学
不利影响
临床终点
来那替尼
肿瘤科
恶心
胃肠病学
实体瘤疗效评价标准
宫颈癌
癌症
进行性疾病
外科
化疗
临床试验
曲妥珠单抗
乳腺癌
作者
Claire F. Friedman,Anishka D’Souza,Diana Bello Roufai,Anna V. Tinker,Marı́a de Miguel,Valentina Gambardella,Jonathan W. Goldman,Sherene Loi,Michelle Melisko,Ana Oaknin,Iben Spanggaard,Geoffrey I. Shapiro,Adam C. ElNaggar,Stefano Panni,Vignesh Ravichandran,Aimee Frazier,Daniel DiPrimeo,Lisa DeFazio-Eli,David B. Solit
标识
DOI:10.1016/j.ygyno.2023.12.004
摘要
Abstract
Objective
HER2 mutations are associated with poor prognosis and are detected in 3–6% of cervical cancers. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, had activity in several HER2-mutant cancer types in the phase 2 SUMMIT basket study. We present updated and final results from the cervical cancer cohort of SUMMIT. Methods
Eligible patients had HER2-mutant, metastatic or recurrent cervical cancer progressing after platinum-based treatment for advanced/recurrent disease. Patients received neratinib 240 mg/day; loperamide was mandatory during cycle 1. Confirmed objective response rate (ORR) was the primary endpoint. Duration of response (DoR), clinical benefit rate (CBR), progression-free survival (PFS), and safety were secondary endpoints. Results
Twenty-two patients were enrolled; 18 (81.8%) had endocervical adenocarcinoma; median two prior systemic chemotherapy regimens (range 1–4). The most common HER2 variant was S310F/Y mutation (n = 13; 59.1%). Four patients had confirmed partial responses (ORR 18.2%; 95% CI 5.2–40.3); 6 had stable disease ≥16 weeks (CBR 45.5%; 95% CI 24.4–67.8). Median DoR was 7.6 months (95% CI 5.6–12.3). Median PFS was 5.1 months (95% CI 1.7–7.2). All-grade diarrhea (90.9%), nausea (54.5%), and constipation (54.5%) were the most common adverse events. Five patients (22.7%) reported grade 3 diarrhea. There were no grade 4 adverse events, no diarrhea-related treatment discontinuations, and two grade 5 adverse events, unrelated to neratinib: dyspnea (n = 1) and embolism (n = 1). Conclusions
Neratinib resulted in durable responses and disease control in patients with HER2-mutant metastatic/recurrent cervical cancer in SUMMIT. These findings support next-generation sequencing and tailored therapy for select patients with advanced cervical cancer. All responses occurred in patients with endocervical adenocarcinoma. Further assessment of neratinib in this setting is warranted. Trial registration number. NCT01953926 (ClinicalTrials.gov), 2013-002872-42 (EudraCT).
科研通智能强力驱动
Strongly Powered by AbleSci AI