Poziotinib in non-small-cell lung cancer patients with HER2 exon 20 mutations: A pooled analysis of randomized clinical trials. Issue 44 (4th November 2022)

• Record Type: Journal Article
• Authors: Wang, Bi-Cheng; Kuang, Bo-Hua; Liu, Xin-Xiu; Lin, Guo-He
• Is Part Of: Medicine. Volume 101:Issue 44(2022)
• Page Start: e31337
• Publication Date: 2022-11-04
• Subjects: HER2 exon 20 mutant -- non-small-cell lung cancer -- pooled analysis -- poziotinib; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000031337
• Languages: English
• ISSNs: 0025-7974

Abstract

Abstract : Background: Non-small-cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 ( HER2 ) exon 20 mutant occurs in 3% of NSCLCs. Targeted agents for this population remain an unmet need. In this analysis, we pooled-analyzed the efficacy and safety of poziotinib, a novel tyrosine kinase inhibitor, in HER2 exon 20 mutant NSCLC. Methods: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were systematically searched on March 9, 2022. The primary endpoints were objective response rate (ORR) and disease control rate. The secondary endpoint was treatment-related adverse events. Results: Three prospective clinical trials, involving 126 patients, were identified. The pooled ORR and disease control rate of poziotinib in HER2 exon 20 mutant NSCLC were 27% (95% CI, 19–35) and 72% (95% CI, 64–80), respectively. Patients with G778_P780dupGSP had the highest ORR (88%; 95% CI, 33–100; n = 12), followed by Y772_A775dupYVMA (20%; 95% CI, 12–30; n = 88) and G776delinsVC (19%; 95% CI, 0–50; n = 13). The most common grade 3 to 4 treatment-related adverse events were skin rash (36%), diarrhea (23%), and oral mucositis (13%). Conclusion: Poziotinib demonstrates moderate antitumor activity in previously treated HER2 exon 20 mutant NSCLC patients with a manageable safety profile. In addition, different subgroup mutations show various benefits of poziotinib treatment. Large-scale and multiarm clinical trials are warranted to confirm a suitable population and therapeutic strategies.