Background: Erb-b2 receptor tyrosine kinase 2 (ErbB2/HER2) mutation has been found in approximately 2-4% of non-small cell lung cancer (NSCLC) patients and has been identified as one of carcinogenic mutations. Afatinib, a member of irreversible HER family inhibitor, has been investigated by a number of literatures, yet whose therapeutic efficiency remains uncertain in NSCLC with HER2 mutation. To elucidate the clinical efficacy and safety of afatinib in treating HER2 mutant NSCLC, we integrated and reanalyzed the data from current available studies.
Methods: We conducted a systematic literature search for published articles regarding afatinib treating HER2-mutant lung cancer. Eight studies met the inclusion and exclusion criteria. The main outcomes were the objective response rate (ORR) and disease control rate (DCR).
Results: Ninety-five patients with HER2 mutations were identified from eight studies. The pooled ORR was 21% (95% CI: 11-34%) and the pooled DCR was 66% (95% CI: 57-76%). The patients harboring A775-G776ins YVMA mutation, the most common subtype of HER2 exon 20 mutation, derived greater clinical benefit. Most adverse events were grade 1-2, except a case of fatal acute renal injury, possibly related to afatinib.
Conclusions: Afatinib monotherapy demonstrated frustrating anti-tumor activity with tolerable toxicity in HER2 mutant NSCLC. Based on current available data, we do not recommend the regular application of afatinib in NSCLC with HER2 mutations unless the response heterogeneity with specific genomic variant of HER2 mutation was further clarified.
Keywords: Afatinib; HER2 mutation; meta-analysis; non-small cell lung cancer (NSCLC).
2020 Translational Cancer Research. All rights reserved.