OBJECTIVES: Treatment of patients with HER2+ eBC usually involves surgery and radiotherapy, often with chemotherapy and HER2-targeted treatment before surgery (neoadjuvant/pre-operative therapy) and/or after surgery (adjuvant/post-operative therapy). Patients who achieve complete pathologic response (pCR) after neoadjuvant therapy have better prognosis. Pertuzumab (P) and trastuzumab (H) are humanized monoclonal antibodies, and when combined together, provide an increased blockade of the HER2 pathway leading to improved pCR rate and survival. The aim of this study was to evaluate cost-effectiveness of P+H combination compared to H in pre– and postoperative setting from payers´ perspective in the Czech Republic.

METHODS: We used a Markov model, sourcing clinical evidence for pre- and post-operative states from following trials: KATHERINE for demographic characteristics, transition probabilities in invasive disease-free survival (iDFS) for non-pCR patients and utility values in eBC, BERENICE and HannaH for pCR rates, and a pooled analysis by Swain et al. 2021 for event-free survival (EFS) hazard ratios (HR) of P+H vs H for pCR patients and EFS HR of pCR vs non-pCR patients. For metastatic states, evidence from EMILIA and CLEOPATRA trials was used. The costs for (neo)adjuvant therapies, subsequent therapies, adverse events and other costs were adapted locally. To test robustness of the results, we also conducted cost-effectiveness analysis with underlying EFS from the pooled analysis with EFS HR from KATHERINE.

RESULTS: Over a time horizon of 51 years with 3% discounting, P+H generated 0.62 incremental QALYs with €9,909 of additional costs compared to H with ICER of €15,966 per QALY in the base case. The alternative scenario resulted in 0.77 incremental QALYs and €7,948 of incremental costs with ICER of €10,336 per QALY.

CONCLUSIONS: Add-on pertuzumab to (neo)adjuvant therapy has clear clinical benefits with acceptable incremental costs. Thanks to the robustness of the results, the Czech HTA agency approved reimbursement of pertuzumab in this indication.