Abstract P6-08-01: A cost-consequence analysis of pertuzumab in the neoadjuvant treatment of high-risk HER2+ Early-Stage Breast Cancer (EBC): health-economic considerations for drug availability in Italy

Abstract Introduction: Neoadjuvant pertuzumab+trastuzumab+chemotherapy (TPC) combo is a well established treatment for HER2+ high-risk (EBC) as recommended by International and National guidelines. However, notwithstanding EMA approval, in some European countries (i.e Italy and France) pertuzumab drug-access is prevented by the NHS decision not to reimburse the drug in a value-driven sustainability balance. This study aims to estimate the cost and consequences of TPC vs. the same combo w/o pertuzumab (TC) in the neaodjuvant treatment of high-risk HER2+ eBC to better understand the value of TPC regimen. Methods: With a Markov model, we simulated the costs and consequences associated to TPC or TC neoadjuvant treatments, using 5 years time horizon and Italian Lombardy region Health System point of view. The model includes nine health states: Neoadjuvant treatment; Surgery; Invasive disease-free Survival (IDFS) with pathological complete response (pCR), IDFS with residual disease (RD), non-metastatic recurrence, remission, first-line treatment and subsequent-lines for metastatic cancer, and death. Transition probabilities and utilities were derived from relevant clinical trials and literature. For each neoadjuvant treatment, the model estimates: direct (drug, administration, hospitalization, disease management), indirect (patients’ loss of productivity), total costs and different outcomes, as cumulative incidence of metastatic recurrence, days of work lost, days with activity impairment, IDFS life years, and quality adjusted life years (QALY). Costs and outcomes were estimated per 100-treated patients. An alternative scenario analysis with a 10-year time horizon and a deterministic sensitivity analysis was performed to assess the impact of model time horizon and parameters value. Results: The estimated costs and outcomes for TPC and TC are reported in Table 1. TPC produces a total direct cost reduction of €75,630 per 100-treated patients, a small increase of TPC neoadjuvant treatment costs (+4.8%) is offset by the lower cost of metastatic treatment and management (-20.4%). Considering also the indirect costs, TPC is associated to a cost reduction of €124,956 per 100-treated patients. The cost saving is associated to a reduction of 5-year cumulative incidence metastatic recurrence (8.32% vs 10.42%, -20.14%), a reduction of days of work loss (-548 days) and days with activity impairment (-283 days) and a 10.5 QALY gained per 100-treated patients. Using a 10-year time horizon, the value of TPC compared to TC increases. Probabilities of pCR with TPC and TC were the parameter with the higher impact on model results. Conclusion: Use of TC instead of TPC in high-risk HER2+ EBC derives a marginal savings (4.8%) according to the first year of our cost-consequence analysis. However, this negligible savings comes with the need for a heavily and long-lasting adjuvant cytotoxic therapy escalation because of a lower clinical activity of TC vs TPC. Moreover, according to medium-term cost-consequence analysis (5 years) the early negligible savings is overwhelmed by the subsequent increase in costs for the patients’ management, because of the lower clinical efficacy of TC vs. TPC. In Italy, the lack of pertuzumab in the neoadjuvant setting of high-risk HER2+ eBC is questionable; our results support the opportunity to reconsider the pertuzumab availability in Italy and reduce inequalities within Europe. Cost and consequences of neoadjuvant treatments for high-risk HER2-Positive Early-Stage Breast Cancer: trastuzuamb+pertuzumab+chemotheraphy (TPC) vs trastuzumab+chemotheraphy (TC) IDFS, Invasive disease-free Survival; QALY, quality adjusted life years. Citation Format: Alberto Zambelli, Marina Elena Cazzaniga, Nicla La Verde, Elisabetta Munzone, Ippazio Cosimo Antonazzo, Lorenzo Giovanni Mantovani, Anna Mancuso, Daniele G. Generali, Paolo Angelo Cortesi. A cost-consequence analysis of pertuzumab in the neoadjuvant treatment of high-risk HER2+ Early-Stage Breast Cancer (EBC): health-economic considerations for drug availability in Italy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-08-01.