Poziotinib in Non–Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial

• DOI: 10.1200/jco.21.01323
• Publication Date: 2021-11-29T20:59:15Z
• Authors: Xiuning Le; Robin Cornelissen; Marina Garassino; Jeffrey M. Clarke; Nishan Tchekmedyian; Jonathan W. Goldman; Szu-Yun Leu; Gajanan Bhat; Francois Lebel; John V. Heymach; Mark A. Socinski
• Keywords: Tolerability; Clinical endpoint; Progression-free survival

Insertion mutations in Erb-b2 receptor tyrosine kinase 2 gene (ERBB2 or HER2) exon 20 occur 2%-5% of non-small-cell lung cancers (NSCLCs) and function as an oncogenic driver. Poziotinib, a inhibitor, was evaluated previously treated patients with NSCLC HER2 insertions.ZENITH20, multicenter, multicohort, open-label phase II study, poziotinib advanced metastatic NSCLC. In cohort 2, received (16 mg) once daily. The primary end point objective response rate by independent review committee (RECIST v1.1); secondary outcome measures were disease control rate, duration response, progression-free survival, safety tolerability. Quality life assessed.Between October 2017 March 2021, 90 median two prior lines therapy (range, 1-6) treated. With follow-up 9.0 months, 27.8% (95% CI, 18.9 to 38.2); 25 achieved partial response. Disease 70.0% 59.4 79.2). Most (74%) had tumor reduction (median 22%). Median survival 5.5 months 3.9 5.8); 5.1 4.2 5.5). Clinical benefit seen regardless types therapy, presence central nervous system metastasis, mutations. Grade 3 higher treatment-related adverse events included rash (48.9%), diarrhea (25.6%), stomatitis (24.4%). dose reductions (76.7%), relative intensity 71.5%. Permanent treatment discontinuation because occurred 13.3% patients.Poziotinib demonstrates antitumor activity insertion