RESUMO
HER2 mutations, which account for 2-4% of non-small cell lung cancer (NSCLC), are distinct molecular alterations identified via next generation sequencing (NGS). Previously, treatment outcomes in HER2-mutant metastatic NSCLC were dismal, showing limited clinical benefit with platinum-based chemotherapy with or without immunotherapy. In contrast to HER2-altered breast and gastric cancer, HER2-mutant NSCLC does not benefit from HER2 targeting agents such as trastuzumab or TDM1. HER2 mutations are also inherently different from HER2 overexpression and amplification. Currently, trastuzumab deruxtecan, a HER2 targeting antibody drug conjugate (ADC) is the first and only approved treatment option for patients with HER2-mutant metastatic NSCLC after failure with standard treatment. In this review, we summarized the biology of HER2 and detection of HER2 overexpression, amplification and mutations, as well as general landscape of landmark and ongoing clinical trials encompassing from chemotherapy to targeted agents, including tyrosine kinase inhibitors (TKIs), ADCs and investigational agents.
Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptor ErbB-2/genética , Trastuzumab/genética , Trastuzumab/uso terapêutico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , MutaçãoRESUMO
Differences in efficacy and toxicity between Asian and Caucasian patients with lung cancer treated with systemic chemotherapy is increasingly recognised. This is a major concern in the clinical setting as it influences outcomes and affect international harmonization of drug development. Interindividual variability of pharmacokinetics, where different genetic polymorphisms affect drug metabolism, transport, and receptor binding may account for the ethnic differences. Treatment efficacy and outcomes may also be explained by differences in diet and lifestyle, access to healthcare, cultural barriers and environmental exposure. Efforts made to design prospective studies investigating ethnic specific determinants to systemic therapy and individualise lung cancer treatment based on genetic makeup of patient are important.
