Poziotinib in non-small-cell lung cancer patients with HER2 exon 20 mutations: A pooled analysis of randomized clinical trials

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. Largescale and multiarm clinical trials are warranted to confirm a suitable population and therapeutic strategies.Abbreviations: DCR = disease control rate, HER2 = human epidermal growth factor receptor 2, NSCLC = non-small-cell lung cancer, ORR = objective response rate, PFS = progression-free survival, PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-analyses, T-DXd = trastuzumab deruxtecan, TRAE = treatment-related adverse events.

HER2 Alterations in Non-Small Cell Lung Cancer: Biologico-Clinical Consequences and Interest in Therapeutic Strategies

“…Consistently, the ORR was 27% with a median PFS of 5.5 months and a median OS of 15 months despite a heavily pre-treated cohort (53% were in the second line or more). These three prospective clinical trials were pooled in a recent meta-analysis published in 2022, confirming the antitumor activity in HER2 exon-20 mutant NSCLC patients [122].…”