For patients with HER2-positive metastatic breast cancer (MBC) who have experienced tyrosine kinase inhibitor (TKI) failure, treatment options include novel anti-HER2 antibody-drug conjugates (ADCs) and the combination of pertuzumab and trastuzumab (HP) with chemotherapy. Prior investigations by our group demonstrated considerable efficacy of novel anti-HER2 ADCs in this population. However, no direct comparative data exist evaluating novel anti-HER2 ADCs versus HP plus chemotherapy. This study aimed to assess and contrast the efficacy and safety of these two therapeutic approaches in patients after TKI failure. Patients with HER2-positive MBC treated with either novel anti-HER2 ADCs or HP combined with chemotherapy from January 2019 to August 2023, all with prior TKI exposure, were included. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), and safety profiles.
Among 150 eligible patients, 83 received novel anti-HER2 ADCs (36 with trastuzumab deruxtecan [T-Dxd] and 47 with other ADCs), and 67 received HP with chemotherapy. Median PFS was 7.0 months in the ADC group and 8.9 months in the HP+chemotherapy group, with ORRs of 51.8% versus 26.9% and CBRs of 69.9% versus 65.7%, respectively. Subgroup analysis indicated improved PFS with T-Dxd compared to HP plus chemotherapy. The most frequent grade 3–4 adverse events were neutropenia and gastrointestinal toxicity in both cohorts. In HER2-positive MBC patients following TKI failure, both novel anti-HER2 ADCs and HP combined with chemotherapy provide moderate efficacy with manageable toxicity. Novel anti-HER2 ADCs are recommended as the preferred option, while HP plus chemotherapy remains a viable alternative, particularly where ADCs are less accessible.
