Efficacy of tucatinib, trastuzumab, and capecitabine (TTC) following trastuzumab-deruxtecan (T-DXd) in HER2-positive metastatic breast cancer (MBC): Updated results and subgroup analyses from the UNICANCER multicenter retrospective cohort.

Abstract

1030 Background: T-DXd is the standard second-line treatment for HER2-positive MBC with TTC being the preferred third-line option. However, the efficacy of TTC following T-DXd remains unclear. Here, we provide an updated and subgroup analysis of a French cohort comprising 101 patients who received TTC after T-DXd. Methods: We conducted a retrospective study across 12 French comprehensive cancer centers, including patients with HER2-positive MBC treated with TTC after T-DXd exposure. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS) and time to next treatment (TTNT). Results: A total of 101 patients who initiated TTC between August 2020 and December 2022 were included in the analysis. The median age was 56.4 years (range: 30.8–84.8). Patients had received a median of 4 prior MBC therapies (range: 2–15), which included pertuzumab (81%) and T-DM1 (93%). 82 patients (81%) experienced progression on T-DXd, while 19 discontinued due to toxicity or other reasons. The data cutoff date was December 1, 2024. For the whole population, with a median follow-up of 29.6 months (95% CI [26.0–34.0]), the median PFS was 4.7 months (95% CI [3.9–5.8]), the median TTNT was 5.2 months (95% CI [4.5–6.6]), and the median OS was 13.9 months (95% CI [12.4–19.0]). For the 86 patients who initiated TTC immediately after T-DXd, the median PFS and TTNT were 5.2 months (95% CI [4.4–6.4]) and 5.5 months (95% CI [4.7–7.2]), respectively. HR+ disease was identified in 71.3% (n=72) of the cohort, with 84.7% receiving TTC immediately post-T-DXd. With a median follow-up of 29.6 months (95% CI [25.1–NR]), the HR+ population had a median PFS of 4.1 months (95% CI [3.5–5.6]) and a median OS of 13.4 months (95% CI [12.3–19.0]). The median TTNT was 4.7 months (95% CI [4.0–6.3]). Among the 65 RECIST-evaluable HR+ patients, best response included progressive disease in 40%, stable disease in 29%, partial response in 29%, and complete response in 2%. With a median follow-up of 29.3 months (95% CI [26.0–NR]), the HR- population had a median PFS of 5.8 months (95% CI [4.4–10.5]) and a median OS of 17.5 months (95% CI [10.6–22.9]). The median TTNT was 6.0 months (95% CI [4.9–10.7]). Among the 24 RECIST-evaluable HR- patients, best response included progressive disease in 25%, stable disease in 38%, partial response in 33%, and complete response in 4%. Conclusions: This large retrospective cohort with extended follow-up highlights the efficacy of TTC in HER2-positive MBC patients previously treated with T-DXd. These findings support the role of TTC as a viable treatment option post-T-DXd and provide insights for optimizing therapeutic strategies in this setting.