The efficacy of ado-trastuzumab emtansine in patients with ERBB2-aberrant non-small cell lung cancer: a systematic review

BACKGROUND: ERBB2 aberrations are oncogenic alterations in lung cancer. However, the reported therapeutic efficacy of ado-trastuzumab emtansine (T-DM1) varied. We therefore evaluated the efficacy and safety of T-DM1 in treating different types of ERBB2 aberrations. METHODS: We conducted a systematic search for original articles and meeting abstracts about ERBB2-aberrant lung cancer treating with T-DM1 in PubMed and EMBASE databases from inception to June, 2020. Statistical analysis was carried out in R software. RESULTS: A total of 120 patients with various ERBB2 aberrations were identified in five studies. ERBB2 upregulation (gene amplification and/or protein overexpression) was more common in smokers with adenocarcinoma, whereas mutations were more common in female non-smokers with adenocarcinoma. The overall objective response rate (ORR) for ERBB2 aberrations was 29% [95% confidence interval (CI): 15–56%]. Subgroup analysis showed an ORR of 41% (95% CI: 11–70%) for ERBB2 gene mutation, 66% (95% CI: 11–100%) for ERBB2 gene amplification, and 3% (95% CI: 0–9%) for ERBB2 protein overexpression. Notably, the ORR was 44% (95% CI: 25–63%) upon concomitant ERBB2 upregulation and mutation. Furthermore, the ORR was 26% (95% CI: 0–54%) for protein overexpression plus gene mutation but up to 80% (95% CI: 50–100%) for triple aberrations: gene amplification plus protein overexpression and gene mutation. CONCLUSIONS: Collectively, T-DM1 might be a critical agent targeting ERBB2 mutated or/and amplified lung cancers.