Cost-Effectiveness of Subcutaneous Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf for the Treatment of High-Risk, HER2-Positive Early Breast Cancer

Findings from modeling studies support adjuvant continuation of pertuzumab plus trastuzumab for patients achieving pathologic complete response among patients with high-risk, HER2-positive early breast cancer.

For patients with high-risk, HER2-positive early breast cancer (EBC), standard neoadjuvant therapy is dual-targeted therapy with pertuzumab plus trastuzumab plus chemotherapy, followed by adjuvant pertuzumab plus trastuzumab for 1 year in patients who achieve pathologic complete response (pCR), whereas patients with residual disease receive ado-trastuzumab emtansine (T-DM1). A new formulation of subcutaneous pertuzumab, trastuzumab, and hyaluronidase-zzxf was recently approved for use in this setting. Modeling studies assessed the cost-effectiveness of the new formulation compared with standard strategy; the results of this study were reported at the 2021 American Society of Clinical Oncology Annual Meeting.

Using a 6-state Markov model, EBC costs and quality-adjusted life-years (QALYs) from a healthcare sector perspective over a lifetime time horizon were assessed. Two EBC treatment strategies were modeled: (1) a new intervention of neoadjuvant therapy with subcutaneous pertuzumab, trastuzumab, and hyaluronidase-zzxf plus chemotherapy with adjuvant continuation if pCR is achieved, and T-DM1 if not; and (2) standard strategy of neoadjuvant infused pertuzumab, trastuzumab plus chemotherapy with adjuvant infused trastuzumab if pCR is achieved, and T-DM1 if not. Event-free survival was derived from the PEONY trial and invasive-disease–free survival from the KATHERINE/APHINITY trials. Utility values were derived from KATHERINE European Quality of Life Five Dimension instrument data, drug prices from wholesale acquisition costs and procedure costs claims analyses. Comparator costs using both biosimilar and branded trastuzumab pricing were assessed. The primary outcome was the incremental cost-effectiveness ratio (ICER). Outcomes were discounted at 3% per year and costs were presented in 2020 US dollars. Uncertainty in outcomes was assessed through Monte Carlo simulation (1000 replicates).

Modeling results showed that the intervention strategy resulted in a gain of 0.092 QALYs. When biosimilar trastuzumab pricing was applied in the standard (base case), the intervention increased costs by $7575 (ICER = $81,793). When branded trastuzumab pricing was applied in the standard (scenario analysis), the intervention increased costs by $982 (ICER = $10,602). Probabilistic analyses showed that the intervention was favored in 52% of simulations at a willingness-to-pay of $100,000/QALY with biosimilar pricing and 81% with branded trastuzumab pricing.

The findings of the modeling studies support adjuvant continuation of pertuzumab plus trastuzumab among patients achieving pCR. Irrespective of whether the comparator uses biosimilar or branded trastuzumab, the new interventional strategy of neoadjuvant pertuzumab, trastuzumab, and hyaluronidase-zzxf plus chemotherapy with adjuvant continuation of dual-targeted therapy is expected to be more cost-effective (<$100,000/QALY) compared with the standard strategy of neoadjuvant pertuzumab and trastuzumab plus chemotherapy with adjuvant trastuzumab continuation for patients with high-risk, HER2-positive EBC.

Source: Sussell J, Roth JA, Hansen S, et al. Cost-effectiveness of subcutaneous pertuzumab, trastuzumab, and hyaluronidase-zzxf for the treatment of high-risk HER2+ early breast cancer. J Clin Oncol. 2021;39(suppl_15):e18846.