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Cost-Effectiveness of Subcutaneous Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf for Early Breast Cancer

Neoadjuvant pertuzumab, trastuzumab, and hyaluronidase-zzxf plus chemotherapy is expected to be cost-effective vs neoadjuvant pertuzumab and trastuzumab plus chemotherapy for patients with high-risk HER2-positive early breast cancer, irrespective of use of biosimilar or branded trastuzumab, according to a study presented at the virtual 2021 ASCO Annual Meeting.

“Recently, a subcutaneously administered formulation of [pertuzumab], [trastuzumab], and hyaluronidase-zzxf… was approved for use in the US,” explained Jesse Sussell, PhD, Genentech, Inc, South San Francisco, CA, and colleagues.

This study aimed to assess the value of the subcutaneous formulation of pertuzumab, trastuzumab, and hyaluronidase-zzxf for the treatment of high-risk HER2-positive early breast cancer.

A six-state Markov model was developed to assess costs and quality-adjusted life years (QALYs) from a health care sector perspective over a lifetime horizon.

Two strategies were modeled. The first strategy (intervention) was neoadjuvant therapy with subcutaneous pertuzumab, trastuzumab, and hyaluronidase-zzxf plus chemotherapy with adjuvant continuation if a pathological complete response (pCR) is achieved, and ado-trastuzumab emtansine (T-DM1) if not. The second strategy (comparator) was neoadjuvant therapy with infused pertuzumab, trastuzumab plus chemotherapy with adjuvant infused trastuzumab if pCR is achieved, and T-DM1 if not.

Researchers derived event-free survival from the PEONY trial and invasive-disease free survival from the KATHERINE/APHINITY trials. Utility values were derived from KATHERINE EQ-5D data, drug prices from Wholesale Acquisition Costs, procedure costs from claims analyses. Comparator costs were assessed using both biosimilar and branded trastuzumab pricing.

The primary outcome was the incremental cost-effectiveness ratio (ICER). Outcomes were discounted at 3% per year and costs are presented in 2020 US dollars.

The intervention strategy resulted in a gain of 0.092 QALYs. With biosimilar trastuzumab in the comparator strategy, the invention increased costs by $7575, with an ICER of $81,793. With branded trastuzumab in the comparator, the intervention increased costs by $982 with an ICER of $10,602.

At a willingness-to-pay threshold of $100,000 per QALY, probabilistic analyses favored the intervention in 52% of simulations with biosimilar trastuzumab pricing and 81% of simulations with branded trastuzumab pricing.

This study provides additional evidence to support adjuvant continuation of [pertuzumab plus trastuzumab] among patients achieving pCR,” wrote Dr Sussell and colleagues, concluding that neoadjuvant pertuzumab, trastuzumab, and hyaluronidase-zzxf plus chemotherapy is expected to be cost-effective for high-risk HER2-positive early breast cancer.


Sussel 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. Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract e18846.

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