HLX02, Pertuzumab, Chemotherapy Combination Effective, Safe in Advanced HER2-Positive Breast Cancer

A combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited efficacy and favorable safety as second and beyond line therapy in patients with HER2-positive metastatic breast cancer.

From March 2020 to December 2021, a Beijing Cancer Hospital held a prospective, single-arm, single-center, phase 2 clinical trial. Eligible participants included patients diagnosed with metastatic breast cancer who were previously treated with trastuzumab alone but experienced disease progression during or after therapy.

Based on the physician, patients were assigned trastuzumab (HLX02), pertuzumab and chemotherapy at baseline. Trastuzumab (HLX02) was administered intravenously as an 8 mg/kg loading dose followed by 6 mg/kg maintenance doses every 3 weeks. Pertuzumab was administered intravenously as an 840 mg loading dose followed by 420 mg maintenance doses every 3 weeks.

Every 6 weeks, tumor assessment was computed with a tomography scan of the chest and if the disease progressed after 6 months, the investigator made the decision on whether to continue chemotherapy or not. Trastuzumab and pertuzumab continued to be administered until disease progressed or toxicity became intolerable to patients.

Study results found treatment was well tolerated among participants. A total of 45 patients were included in the data with a median age of 56 years. Of the total number of patients, 12 (26.7%) were treated in second line, while 33 (73.3%) were treated in third line and later settings.

The primary endpoint of the study was the progression free survival (PFS), which was calculated from the time of first administration to the time of disease progression or death. Follow-up consisted of an average of 24.4 months, with 35 of the 45 patients enduring PFS events for about 7.6 months. There were no major differences observed in the subgroup analysis for PFS.

Overall survival, a secondary endpoint of the study calculating the time of the first administration to the time of death due to any cause, was unable to be reached due to the short follow-up period.

Another secondary endpoint of the study, objective response rate (ORR), was defined as the proportion of patients with measurable disease whose best overall response was evaluated as either complete remission (CR) or partial remission (PR). At the end of the study, 14 (31.1%) patients achieved PR, 27 (60%) had stable disease, and 4 (8.9%) had progressive disease. None of the patients had a CR.

Lastly, the disease control rate (DCR) was a secondary endpoint defined as the proportion of patients who achieved CR, PR, and stable disease (SD). Patients achieved a 31.1% ORR with a 91.1% DCR.

The safety profile of the treatments found most toxicities were grade 1 or 2 and manageable. The most common adverse events were neutropenia (n = 20 patients; 44%), anemia (n = 9; 20%), diarrhea (n = 9; 20%), and alanine aminotransferase/aspartate aminotransferase elevation (n = 8; 17.8%).

Adverse events graded a 3 or higher, mainly neutropenia patients (n = 3; 6.7%), were ruled to mainly be associated with chemotherapy instead of trastuzumab or pertuzumab. Overall, the study regimen did not exhibit any unexpected toxicities.

The study's main limitation was the single arm, single center study design. Additionally, the follow-up period was not long enough to allow for an overall survival analysis.

Authors concluded that their findings provide new evidence for treatment of dual-antibody therapy in late-line settings of patients with HER2-positive metastatic breast cancer.

Reference

Zhang R, Liu X, Song G, Zhang Y, Li H. Trastuzumab biosimilar (HLX02), pertuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer after progression of trastuzumab: A prospective, phase II study. Cancer Res Treat. Published online December 20, 2023. doi:10.4143/crt.2023.1151