What question did this study set out to answer?

This study investigates whether the choice of antiemetic regimen affects overall survival in patients with metastatic HER2-positive breast cancer receiving trastuzumab deruxtecan.

February 19, 2026

Abstract PS5-01-11: Impact of antiemetic strategy on overall survival in patients with metastatic HER2-positive breast cancer treated with trastuzumab deruxtecan: A real-world retrospective study

Key Points

This study investigates whether the choice of antiemetic regimen affects overall survival in patients with metastatic HER2-positive breast cancer receiving trastuzumab deruxtecan.
Conducted a retrospective cohort study using the IntegraConnect database of cancer patients.
Included patients who initiated trastuzumab deruxtecan from December 2019 to October 2024.
Compared two antiemetic regimens: NK1 + 5HT3 + dexamethasone and 5HT3 + dexamethasone.
Employed Kaplan-Meier analysis for survival assessment and multivariable Cox models for confounder adjustment.
Patients receiving the NK1-based regimen had a median overall survival of 35.7 months compared to 19.2 months for the 5HT3 + dexamethasone group (P<0.01).
Median time to treatment discontinuation was longer in the NK1 group (16.0 months) versus the 5HT3 group (11.0 months, P<0.01).
At 12 months, 63% of NK1 patients remained on treatment compared to 48% of those on the 5HT3 regimen.
Multivariable analysis indicated a 40% reduced risk of discontinuation or death with the NK1 regimen compared to the 5HT3 + dexamethasone regimen.

Abstract

Abstract Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) approved for the treatment of metastatic HER2-positive (HER2+) breast cancer in the second-line of therapy or later and has shown significant improvements in progression-free and overall survival (OS) in this population. However, T-DXd is also associated with gastrointestinal toxicities, including nausea and vomiting, which can adversely affect quality of life and treatment adherence. While antiemetic guidelines recommend the use of combination prophylaxis for agents with moderate to high emetogenic potential, there is limited evidence on whether antiemetic strategies themselves impact treatment duration and survival outcomes in oncology patients (pts) receiving T-DXd. This real-world study investigates the potential association between antiemetic regimen choice and OS in metastatic HER2+ breast cancer pts initiating T-DXd therapy. Methods: The IntegraConnect PrecisionQ de-identified electronic health record database, consisting of 3 million cancer pts across 500 care sites, was used to conduct a retrospective cohort study of 540 pts with metastatic HER2+ breast cancer who initiated trastuzumab deruxtecan between December 20, 2019 and October 31, 2024. Pts were stratified by their antiemetic regimen within 7 days of T-DXd initiation: Group 1 (n=251) received 5HT3 receptor antagonist + dexamethasone and Group 2 (n=289) received NK1 receptor antagonist + 5HT3 receptor antagonist + dexamethasone. Real-world overall survival (rwOS) and time to treatment discontinuation or death (TTD) were assessed using Kaplan-Meier analysis starting from the time of T-DXd initiation. Multivariable Cox proportional hazards models were used to adjust for potential confounders including age at diagnosis, race, Eastern Cooperative Oncology Group (ECOG) performance status, and line of therapy. Results: Baseline demographics were balanced between groups. Median age at diagnosis was 54 years for Group 1 and 55 years for Group 2; median age at T-DXd initiation was 61 years for Group 1 and 62 years for Group 2. Both groups were predominantly White (60.2% in Group 1 and 66.4% in Group 2). Median TTD (16.0 vs. 11.0 months (log-rank P 0.01) and median rwOS (35.7 vs. 19.2 months (log-rank P0.01) were significantly longer in Group 2 (NK1-based regimen) compared to Group 1 (5HT3 + dexamethasone). The probability of remaining on treatment at 12, 24, and 36 months was higher in Group 2: 12 months: 63% vs. 48%, 24 months: 38% vs. 20%, 36 months: 27% vs. 8%. Similarly, estimated survival at 12, 24, and 36 months was higher in Group 2: 12 months: 83% vs. 71%, 24 months: 60% vs. 42%, 36 months: 48% vs. 29%. On multivariable analysis, receipt of the NK1-containing regimen was associated with a 40% reduced risk of discontinuation or death (hazard ratio: 0.60, 95% CI: 0.45-0.80; P0.01) compared to the 5HT3 + dexamethasone group, independent of other covariates. Poorer ECOG performance status was associated with increased likelihood of discontinuing T-DXd and worse survival. Conclusion: Among pts with metastatic HER2+ breast cancer treated with T-DXd, the use of a 3-drug antiemetic regimen including a NK1 receptor antagonist + 5HT3 receptor antagonist + dexamethasone was associated with significantly longer treatment persistence which seems to translate to improved OS compared with a 2-durg antiemetic regimen of a 5HT3 receptor antagonist + dexamethasone. These findings suggest that optimization of supportive care strategies may have survival implications and merit further evaluation/prospective validation. Citation Format: S. Reganti, R. Choksi, F. Kudrik, D. Patt, S. Reddy, S. Rosenfeld, D. Parris, G. Rahimi, A. Rui, M. Gart, C. Wall, B. Wang, P. Varughese, J. Donegan, L. Morere, R. Geller, J. Scott, V. Gorantla. Impact of antiemetic strategy on overall survival in patients with metastatic HER2-positive breast cancer treated with trastuzumab deruxtecan: A real-world retrospective study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-01-11.

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