Abstract P4-03-19: Expected real-world impact of escalation and de-escalation of Her2-directed therapy in breast cancer patients receiving neoadjvuant therapy
Authors: Mollenthiel Andrew , Morris Aidan , Lauren Corke , Simmons Christine 
Published: March 2023

Abstract
Background: For patients with palpable, early stage, Her2+ breast cancer, neoadjuvant therapy (NAT) is the preferred approach to curative treatment. While Trastuzumab (T) is standardly included in NAT protocols globally, there is variable ability to escalate or potentially de-escalate therapy due to perceived cost/benefit of additional Her2 targeting therapies, such as Pertuzumab (P) in the early stage setting. The impact of neoadjuvant Pertuzumab (NeoP) does have potentially significant impact on the need for therapeutic interventions in the setting of recurrence. It is challenging to estimate the real world impact financially on escalated therapy in the neoadjuvant setting and likewise the long-term effects of cost of recurrent therapy. We wanted to assess and estimate the impact of NeoP addition to T in British Columbian patients with Her2+ early breast cancer, and estimate incremental impact on short and long-term costs to our cancer system. Methods: Utilizing quality assurance database prospectively updated at BC Cancer Vancouver, we extracted cases of patients with Her2+ breast cancer who received NAT between 2012 – 2021 to provide real world estimations of prevalence of cases and estimated annual costs. Descriptive statistics were utilized to calculate rate of pCR in patients receiving neoadjuvant her2 directed therapy. Expected rates of improvement in pCR with the addition of NeoP were extracted from meta-analyses of Her2 directed therapy in the neoadjuvant setting. The publicly available national pCODR Ecomonic Guidance Reports were utilized to identify cost per cycle per patient of Pertuzumab, Trastuzumab, TDM-1 and chemotherapy in the Canadian healthcare system. The additional cost of NeoP per centre, per year, was compared to the current cost of non-Pertuzumab containing neoadjvuant regimen. Based on recurrence data collected from the database, the expected impact of NeoP on rate of recurrence and subsequent need for Her2 directed therapy in the metastatic setting was calculated. Results: 347 patients with HER2+ breast cancer received neoadjuvant T + chemotherapy at the BC Cancer Vancouver Centre between May 2012 and May 2022. 137 patients (39.5%) achieved pCR and 210 (60.5%) did not achieve pCR. Of those who did not achieve pCR, 12% recurred and 6% died, compared to only 5% and 1% respectively in the group that did achieve pCR. Based on a risk ratio of 1.57, we calculated the expected rate of pCR in our real world cohort would have increased from 39.5% to 62.3% with the availability of NeoP routinely. For each year of data in our cohort, an average of 40 patients with Her2 positive disease were treated with neoadjvant therapy. Using modeling based on our real world cohort we predicted an added cost of $669,920 to provide neoadjuvant pertuzuamb at one Canadian Cancer centre per year. Based on extraction of data from current state, where adjvuant TDM-1 is provided for 13 cycles in the setting of no PCR, the adjuvant TDM-1 costs were estimated to be $1, 729, 151 without NeoP and $1,067377 with NeoP. The cost difference for addition of NeoP in the treatment of early Her2+ breast cancer at one Canadian Centre per year was calculated as $8,146 increase in cost. In patients who had recurrence in our cohort we observed a shorter median survival than expected with most patients succumbing to their recurrence within a 2-3 year period. We expanded our modeling to assess the incremental impact on estimated cost of treatment for those who may recur. We estimated a cost saving of $85,054 per centre, per year, related to decrease in risk of recurrence of Her2+ breast cancer in those who receive NeoP. Conclusion: While the additional cost per centre of adding NeoP was $8146, the subsequent decrease in expected rate of recurrence resulted in a cost savings of $85,054.
Citation Format: Andrew Mollenthiel, Aidan Morris, Corke Lauren, Christine Simmons. Expected real-world impact of escalation and de-escalation of Her2-directed therapy in breast cancer patients receiving neoadjvuant therapy. [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 P4-03-19.