Abstract P4-02-05: Predictors of long-term durable response in de novo HER2 positive metastatic breast cancer and the real world treatment experience at two institutions
Authors: Smith Claire E. , Marcom Paul K. , Zahi Mitri , Ko Naomi 
Published: March 2023

Purpose Modern HER2-directed therapies enable some patients with de novo HER2+ metastatic breast cancer (MBC) to achieve long-term, durable responses (DR), which can be defined as no progression of disease since initial diagnosis. Clinical and pathologic factors that predict DR continue to be elucidated. Expert opinion dictates indefinite HER2-directed therapies for patients who achieve DRs, but real-world examples of this practice are lacking in the literature.

Methods This is a retrospective study of all patients with de novo HER2+ MBC at two major academic institutions who received at least one dose of trastuzumab between 2012-2019. DR is defined as absence of progression/death at any point after diagnosis. Controls are patients with evidence of progression/death. Age, ER/PR status, sites of metastasis, surgical resection of primary tumor and initial treatment were analyzed as predictors of DR using an unpaired T test, with p&lt; 0.05 chosen as threshold for significance. For patients with DR, time to complete (CR) and partial response (PR) according to RECIST 1.1 were recorded, as was the duration and treatment patterns surrounding trastuzumab and pertuzumab. Patients were defined as having cardiotoxicity if they experienced a decline in cardiac ejection fraction at any point while on trastuzumab therapy leading to treatment delays or discontinuation.

Results 96 patients with de novo HER2+ MBC, 28 with DR and 68 with progression, were identified. The average follow up of patients with DR was 90 months (range 27-224), compared to 58 months (range 1-208) in controls. The entire cohort of 96 patients had a median PFS of 23.5 months and a median OS of 88 months. Among the 28 patients with DR, 2 achieved stable disease, 10 patients had documented PR at 4 months on average (range 2-6 months), and 26 patients had CR at 7.7 months on average (range 2-19 months). Among patients with DR, nine patients have been receiving trastuzumab for over ten years with no evidence of disease and one patient opted to discontinue trastuzumab. 75% of patients with DR had a single metastatic site, compared with 47% of patients with progression (OR 3.7, p=0.01). 64% of patients with DR received a regimen containing trastuzumab, pertuzumab, and a taxane, while 28% of patients who progressed did (OR 4.5, p&lt; 0.001). 57% of patients with DR underwent surgical removal of breast primary, compared with 24% of patients who progressed (OR 4.3, p=0.002.) Age, and ER/PR status did not predict DR. (Table 1) Six patients (6.3%) developed reduced ejection fraction requiring treatment interruption or cessation, five in the group who progressed, one in the DR group.

Conclusion Nearly a third of patients with de novo HER2+ MBC achieved DR. Factors that correlate with DR include single metastatic site, initial trastuzumab, pertuzumab and taxane therapy, and surgical resection of primary tumor. This suggests that in selected patients, a more aggressive up front approach including surgical resection, and agents such as carboplatin, and trastuzumab deruxtecan deserves further study. Among patients with DR, indefinite trastuzumab administration is the norm with minimal cardiotoxicity but the impact of this on quality of life and financial toxicity are not well described.

Table 1: Clinical characteristics of de novo HER2 positive metastatic breast cancer that predict durable response

Citation Format: Claire E. Smith, Paul K. Marcom, Mitri Zahi, Naomi Ko. Predictors of long-term durable response in de novo HER2 positive metastatic breast cancer and the real world treatment experience at two institutions [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 P4-02-05.