التفاصيل البيبلوغرافية
| العنوان: |
Targeting HER2-mutant metastatic cervical cancer with neratinib: Final results from the phase 2 SUMMIT basket trial. |
| المؤلفون: |
Friedman, Claire F.1,2 (AUTHOR) friedmac@mskcc.org, D'Souza, Anishka3 (AUTHOR), Bello Roufai, Diana4 (AUTHOR), Tinker, Anna V.5 (AUTHOR), de Miguel, Maria6 (AUTHOR), Gambardella, Valentina7 (AUTHOR), Goldman, Jonathan8 (AUTHOR), Loi, Sherene9 (AUTHOR), Melisko, Michelle E.10 (AUTHOR), Oaknin, Ana11 (AUTHOR), Spanggaard, Iben12 (AUTHOR), Shapiro, Geoffrey I.13 (AUTHOR), ElNaggar, Adam C.14 (AUTHOR), Panni, Stefano15 (AUTHOR), Ravichandran, Vignesh1 (AUTHOR), Frazier, Aimee L.16 (AUTHOR), DiPrimeo, Daniel16 (AUTHOR), Eli, Lisa D.16 (AUTHOR), Solit, David B.1 (AUTHOR) |
| المصدر: |
Gynecologic Oncology. Feb2024, Vol. 181, p162-169. 8p. |
| مصطلحات موضوعية: |
*CERVICAL cancer, *CANCER patients, *METASTASIS, *CANCER chemotherapy, *PROTEIN-tyrosine kinase inhibitors |
| مستخلص: |
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. 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. 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). 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). • Somatic HER2 mutations occur in approximately 3–6% of cervical cancers and have been associated with poor prognosis. • Four of 22 patients with HER2 -mutant cervical cancer had a confirmed response to neratinib; ten had clinical benefit. • 13 patients had S310F/Y mutation in line with public datasets; all cervical cancer cohort responders had S310F/Y mutation. • Long-term stable disease was observed across multiple HER2 mutation types. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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