A real-world comparison study of the efficacy of dual-target first-line rescue treatment of human epidermal growth factor receptor 2 positive advanced breast cancer: trastuzumab combined with pertuzumab versus trastuzumab combined with pyrotinib

Introduction: Trastuzumab combined with pertuzumab (HP) is a first-line therapy for advanced breast cancer (ABC). However, trastuzumab combined with pyrotinib (HPyr) could also exert complementary and synergistic effects. Currently, clinical trials directly comparing the effectiveness of the above two treatment approaches are lacking. Herein, a registered single-center, retrospective study (NCT04609540) was caried out. Methods: In the present study, patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive ABC and treated with dual-target first-line rescue treatment at the Shandong Cancer Hospital between January 2018 and February 2023 were included. Patients were assigned to the HP or HPyr treatment groups by the physician-in-charge. The clinical, pathological and prognostic data of all patients were collected and recorded. Results: Among the 89 patients included, 47 received HP, while the remaining 42 HPyr. The therapeutic effect of each treatment approach was determined via evaluating progression-free survival (PFS). The results showed that patients who were treated with HPyr displayed a higher progression rate (71.4% vs. 63.8%) compared with those treated with HP. However, statistical significance was not reached (mean PFS, 21.0±1.9 vs. 24.1±2.8 months; P=0.653). In addition, patients of >60 years old, who received HPyr and younger patients (≤40 years old) who received HP had longer PFS (22.8±4.9 vs. 16.8±4.2 months; P=0.332; and 27.4±5.5 vs. 15.8±5.6 months; P=0.098, respectively). PFS without significant differences was also obtained in the other subgroups. Furthermore, HP showed better clinical efficacy in young patients compared with older ones, while HPyr benefitted older patients. In the other subgroups, the two dual-target regimens also displayed curative effects, without significant differences. Discussion: Overall, the results of the current study suggested that HPyr could be equivalently used as HP, as a first-line treatment strategy for patients with HER2-positive ABC. Currently, more prospective large-sample studies are needed to further validate our conclusions.