Abstract PO3-04-07: Characterization of response to first-line chemotherapy, trastuzumab, and pertuzumab among patients with de novo metastatic HER2-positive breast cancer

Abstract Background: With optimization of treatment for early-stage human epidermal growth factor receptor 2-positive (HER2+) breast cancer, the proportion of patients diagnosed with HER2+ metastatic breast cancer (MBC) who have de novo disease is expected to increase. The standard first-line treatment for HER2+ metastatic breast cancer (MBC) is the combination of a taxane, trastuzumab (H), and pertuzumab (P) based on the CLEOPATRA trial. Complete response (CR) rates with this regimen range from 13-18%; previous exposure to anti-HER2 therapies is associated with worse outcomes. However, rates of CR, clinicopathologic characteristics associated with CR, duration of response, and most common sites of relapse among patients with de novo HER2+ MBC are not well described. Methods: Patients with de novo HER2+ MBC who received first line HP-based therapy between 5/2011 and 2/2023 with genomic sequencing data available were included in this retrospective study. Clinicopathologic characteristics were abstracted from medical records. The primary objectives were to define CR rate and progression-free survival (PFS). For response assessment, radiology reports from imaging studies (PET or CT) following initiation of therapy were utilized and response was categorized as CR, defined as interpretation of “no evidence of disease,” or non-CR. Progression of disease (PD) was defined as increase in disease burden that led to treatment change. Factors associated with CR were examined using Wilcoxon rank sum test, Pearson’s Chi-squared test, and multivariable logistic regression. PFS was defined as time from first dose of therapy to PD or death and was calculated and compared using Kaplan Meier estimate and log-rank test. Results: We identified 705 patients with HER2+ MBC treated with first-line chemotherapy and HP, of whom 212 had de novo presentation. After exclusion of 40 patients due to incomplete treatment information, 172 patients were included in this analysis. Median age was 49. 108 patients (62.8%) had hormone receptor-positive disease. 149 (86.6%) patients were treated with paclitaxel or nab-paclitaxel, 20 (11.6%) patients were treated with docetaxel, and 3 patients (1.7%) were treated with vinorelbine. Response assessment was based on PET scans in 144/172 patients (83.7%) and CT scans in 28/172 patients (16.3%). 79 patients (45.9%) had CR while 93 patients (54.1%) had non-CR. Factors associated with CR included younger age at diagnosis (median age 42 among CR vs. 53 among non-CR, p=0.01) and HER2 3+ immunohistochemistry (p=0.007); hormone receptor-positivity was not associated with CR (65% CR rate among hormone receptor-positive, 63% among hormone receptor-negative, p=0.9). Among patients with CR, median time to CR was 5.5 months (interquartile range 3.6-10.2 months). In the total cohort, median follow-up was 50.9 months. 117 patients (68.0%) have progressed or died; 55 patients remain on first-line treatment. 37/79 (46.8%) of patients with CR have progressed or died and 80/93 (86.0%) of patients with non-CR have progressed or died (p0.001). Median PFS was 21.6 months (95% CI 17.9-29.9) but differed by response; median PFS was 67.2 months (95% CI 49.1-not reached) for patients with CR vs.12.9 months (95% CI 10.2-18.9) for patients with non-CR (p 0.0001). PD by site was as follows: breast/axillary nodes (34.2%), bone only or non-visceral site (25.4%), central nervous system (21.9%), and visceral site (18.4%). Conclusions: Nearly half of patients with de novo HER2+ MBC have CR on first-line chemotherapy and HP; patients with CR have significantly longer PFS compared to patients with non-CR. Future studies evaluating treatment discontinuation following durable CR and the utility of circulating tumor DNA in this setting are needed. Citation Format: Emanuela Ferraro, Atif Khan, George Plitas, Yuan Chen, Mehnaj Ahmed, Julia An, Chau Dang, Mark Robson, Sarat Chandarlapaty, Shanu Modi, Pedram Razavi, Sherry Shen. Characterization of response to first-line chemotherapy, trastuzumab, and pertuzumab among patients with de novo metastatic HER2-positive breast cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-07.