A phase II study of pyrotinib combined with apatinib in first-line treatment of advanced non-small cell lung cancer patients with primary HER-2 mutations/amplification

BackgroundIn recent years, targeted therapy for non-small cell lung cancer (NSCLC) with HER-2 gene mutations has become a focused but difficult issue. However, the efficacy of targeted therapy is not satisfactory, and clinical demands of such patients have not been met yet. Pyrotinib, an oral irreversible HER tyrosine kinase inhibitor (TKI), performs well in NSCLC with primary HER-2 mutations/amplification. Some studies found a synergistic effect of pyrotinib combined with anti-vascular therapy, and front-line therapy could generate more benefits than post-line therapy.MethodsThis single-arm, open-label, prospective phase II study aimed to evaluate the efficacy and safety of pyrotinib combined with an anti-vascular drug apatinib in first-line treatment of advanced NSCLC patients with HER-2 mutations/amplification.This study included advanced NSCLC patients with primary HER-2 mutations or amplification and no previous systemic anti-tumor therapy. All subjects received a treatment with pyrotinib (400mg once daily, oral) and apatinib (250mg once daily, oral) until disease progression, intolerable adverse events or death. Primary endpoint was objective response rate (ORR) evaluated by researchers, secondary endpoints included progression-free survival(PFS), disease control rate (DCR), duration of response (DOR) and safety.ResultsA total of 21 patients were included from November 2021 to December 2023. The last follow-up was on March 15, 2024, with a median follow-up of 11.27 months (95% confidence interval[CI]: 5.93-16.60). Among 21 assessable patients, 15 patients (71.4%) achieved partial response(PR), 5 patients (23.8%) remained stable disease(SD),thus ORR was 71.4% (15/21) and DCR was 95.2% (20/21). Median PFS was 11.93 (95% CI:4.27-19.59) months, median DOR and OS were not reached yet. Grade≥3 treatment-related adverse events were diarrhea (14.3%), neutropenia (4.8%) and elevated AST (4.8%).No treatment-related death was observed.ConclusionsCombination of pyrotinib and apatinib showed great efficacy and acceptable safety in first-line treatment of NSCLC patients with HER-2 alterations. The final result still need further follow-up.Clinical trial identificationChiCTR2100052156, Registration date: 2021-10-20.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.