Efficacy of targeted therapy in patients with HER2-positive non-small cell lung cancer: A systematic review and meta-analysis
Topic: Immunotherapy

Anti-human epidermal growth factor receptor 2 (HER2) therapy is an effective treatment for HER2-positive gastric and breast malignancies. However, the efficacy of HER2-targeted therapy in non-small cell lung cancer (NSCLC) patients with HER2 alterations remains controversial. We searched studies on HER2-targeted therapy in NSCLC patients that reported objective response rate (ORR), disease control rate (DCR) and progressionfree survival (PFS) published from database inception to 30 May 2021. A total of 32 trials involving 958 patients were included. The ORRs of HER2-TKIs targeted therapy, humanised monoclonal antibody, trastuzumab-based treatment and antibody-drug conjugate (ADC) (T-DM1) were 22% (95% CI 11-31), 23% (95% CI 20-65), 26% (95% CI 14-39) and 16% (95% CI _6-37), while that of ADC (DS-8201) was 60% (95% CI 35-85). The DCRs of these groups were 59% (95% CI 49-69), 39% (95% CI _9-88), 63% (95% CI 37-89), 31% (95% CI 4-58) and 87% (95% CI 62-112), respectively. In the subgroup analysis, numerically higher ORRs and DCRs were observed in the poziotinib (38%; 75%) and pyrotinib (35%; 83%) groups. The median PFSs of these groups were 5.51 months, 3.09 months, 4.61 months, 2.65 months and 12.04 months, respectively. HER2-targeted therapy can be considered an acceptable treatment strategy for NSCLC patients with HER2 alterations. In particular, ADC (DS-8201), pyrotinib and poziotinib demonstrated promising anti-tumour activity in HER2-positive NSCLC.

PICO
Population: Patients with HER2-positive non-small cell lung cancer
Intervention: HER2-targeted therapy (Including HER2-TKIs, humanised monoclonal antibody, trastuzumab-based treatment, antibody-drug conjugate (ADC) (T-DM1), and ADC (DS-8201))
Outcomes: Objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS)

Included studies:
title: Pan-cancer landscape and analysis of ERBB2 mutations identifies poziotinib as a clinically active inhibitor and enhancer of T-DM1 activity
title: Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives
title: Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort
title: Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined lung adenocarcinoma
title: Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors
title: HER2 mutations in Chinese patients with non-small cell lung cancer
title: Afatinib in patients with metastatic or recurrent HER2-mutant lung cancers: a retrospective international multicentre study
title: Clinical activity of pan-HER inhibitors against HER2-mutant lung adenocarcinoma
title: Activity of afatinib in heavily pretreated patients with ERBB2 mutation-positive advanced NSCLC: findings from a global named patient use program
title: Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer
title: HER kinase inhibition in patients with HER2- and HER3-mutant cancers
title: Afatinib in NSCLC with HER2 mutations: results of the prospective open-label phase II NICHE trial of European Thoracic Oncology Platform (ETOP)
title: HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib
title: Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter open-label single-arm phase II study
title: Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies
title: Trastuzumab plus docetaxel in HER2/neu-positive non-small-cell lung cancer: a California Cancer Consortium screening and phase II trial
title: Efficacy and safety of single-agent pertuzumab, a human epidermal receptor dimerization inhibitor, in patients with non small cell lung cancer
title: Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a role? Focus on Eastern Cooperative Oncology Group Study 2598
title: Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer
title: Targeted therapy for advanced solid tumors on the basis of molecular profiles: results from MyPathway, an open-label phase IIa multiple basket study
title: Trastuzumab and paclitaxel in patients with EGFR mutated NSCLC that express HER2 after progression on EGFR TKI treatment
title: Targeting HER2 with trastuzumab deruxtecan: a dose-expansion phase I study in multiple advanced solid tumors
title: A phase II study of trastuzumab emtansine in HER2-positive non-small cell lung cancer
title: Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase II basket trial
title: Trastuzumab emtansine (T-DM1) in patients with previously treated HER2-overexpressing metastatic non-small cell lung cancer: efficacy, safety, and biomarkers