Abstract

Abstract Background: Although huge progress has been made in treating HER2-positive metastatic breast cancer in the last decade, it remains an incurable disease. Dual anti-HER2 therapy with pertuzumab and trastuzumab combined with chemotherapy represents the standard first line treatment of metastatic HER2-positive breast cancer, in view of the impressive CLEOPATRA study results. The aim of this study was to analyze the efficacy of dual antiHER2 therapy in real-world clinical practice and determine the differences in the clinicopathological characteristics of the long-term responders in comparison with short-term responders. Methods: Retrospective analysis of dual antiHER2 therapy efficacy was done and correlated to clinical and pathological characteristics of patients with different duration of response (DoR) in the first line metastatic HER2-positive breast cancer. The study was conducted at the UHC Zagreb, Croatia and approved by the Ethics Committee. Long-term responders were defined as patients with a duration of response (DoR) to dual antiHER2 therapy ≥ 36 months, and short-term responders were defined as patients with DoR ≤ 12 months. Progression-free survival was estimated using the Kaplan-Meier method. The reverse Kaplan-Meier method was used to estimate median follow-up duration. The non-parametric Chi-Square test (between categorical variables) and Mann-Whitney U-test (between continuous variables) were used to determine the differences between long-term and short-term responders groups. The significance level was set at p < 0.05. Results: Altogether, 128 patients treated with dual antiHER2 therapy for HER2-positive metastatic breast cancer from October 2015 to May 2022 were included in the study. By data cut-off, 50.8 % (N=63) of patients had progressed or died. The median follow-up time was 36 months. The median PFS was 31 months for the total cohort (95% CI 22.6 -39.3). Overall, 29 patients among the long-term responders and 32 patients in the short-term responders group were identified. A comparison of clinical and pathological characteristics between the two groups is shown in Table 1. Even though patients in the group of long-term responders were younger (54.5 years vs. 56.5 years), had less visceral involvement (69 % vs. 81.3%), and were more often trastuzumab ”naive“ (75.9% vs. 68.7%), no statistically significant differences were found between the two groups. Conclusion: In this real-life study, the median PFS was 31 months for the total cohort, even longer than in the referent CLEOPATRA trial, which confirms the effectiveness of dual antiHER2 therapy in a real-world setting. No possible clinical or pathological predictors of long-term response were identified, but larger studies may be able to distinguish patients’ characteristics associated with long-term response. Table 1: A comparison of clinical and pathological characteristics between the group of long-term responders and short-term responders Citation Format: Marija Križić, Tajana Silovski, Marina Popović, Natalija Dedić Plavetić. Real-world efficaccy of dual antiHER2 therapy in first line metastatic HER2-positive breast cancer and the possibility of prediction of long-term response [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 P4-01-39.

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