Systematic review and single-arm meta-analysis of HER2-targeted monotherapy in HER2-mutant non-small cell lung cancer

HER2-mutant non-small cell lung cancer (NSCLC), most commonly driven by exon 20 insertion, has historically shown limited benefit from early pan-HER2 inhibitors. Multiple HER2-targeted agents have since emerged. A systematic review and single-arm study meta-analysis investigated clinical efficacy of HER2-targeted monotherapies in HER2-mutant NSCLC. Twenty studies (n=1,489) met eligibility criteria. The pooled objective response rate was 51% (95% CI 33-68; I²=89.8%) with limited separation across TKI generations. Median progression-free survival ranged for 5.5 to 11.5 months. Twelve-month overall survival estimates were similar between pyrotinib and trastuzumab deruxtecan. In exon 20-restricted analyses (n=392), the pooled objective response rate was 52% (95% CI 28-74). The authors conclude that next-generation HER2-selective TKIs achieved higher objective response rates than oldere inhibitors, particularly in HER2 exon 20 insertion-mutant disease; however, differences in durability-related outcomes were less distinct in later-line studies.