Advances and Future Perspectives of HER2 Mutations in Non-Small Lung Cancer (NSCLC), Especially in China.

Abstract

HER2-mutated non-small lung cancer (NSCLC) in China represents a substantial patient population characterized by an unfavorable prognosis. However, at present, the main clinical treatment options are relatively limited. HER2 mutations in Chinese NSCLC (2019-2024) demonstrated 3.8%-5.6% prevalence via NGS, exceeding global baselines, with superior detection vs PCR (4.5% vs 3.1%). In addition, more attention was paid to molecular analysis and the detection rate of HER2 genomic alterations in NSCLC patients in eastern and northern China compared to other parts of China, which might be related to regional economic differences and geographic differences in lung cancer epidemiology. The evolving therapeutic landscape has established new-generation TKIs (pyrotinib) and antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (T-Dxd) as targeted strategies for HER2-mutant NSCLC. Despite late research initiation, China rapidly advanced from retrospective analyses to pioneering new drug trials. In general, the incidence of HER2-mutated NSCLC in the Chinese population seems to be higher than the world average, and there is a large number of missed HER2-mutated NSCLC patients in China. In this field, ADCs and novel TKIs are being developed and researched in spurts, and new drugs are moving from back-line therapy to front-line therapy, and from single-drug regimens to combination regimens.