Real-world multicenter study of T-DXd treatment in Chinese patients with metastatic breast cancer

Abstract

Background

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) approved in China for HER2-positive or HER2-low metastatic breast cancer (MBC) patients. Little real-world evidence is available in China. This study aimed to investigate the real-world effectiveness and safety of T-DXd in Chinese MBC patients.

Methods

This study retrospectively enrolled 309 MBC patients treated with T-DXd across 9 institutions nationwide in China between December 2019 and March 2024. T-DXd was administered intravenously at a dose of 5.4 mg/kg on day 1 of a 21-day cycle. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Real-world adverse events (AEs) were graded according to CTCAE 4.0. The study was registered at ClinicalTrials.gov (NCT05594082).

Findings

A total of 309 MBC patients were included, with 168 HER2-positive and 141 HER2-negative patients (133 of HER2-low and 8 of HER2 0). Among HER2-positive and HER2-negative patients, median age was 53.5 and 55.0 years, 14.3% and 17.7% ECOG scores of 2, 83.9% and 84.4% patients with visceral metastases, 32.7% and 23.4% patients with brain metastasis, respectively. The median number of lines of therapy (LOT) for MBC patients receiving T-DXd was 4 for both groups. At the cutoff date of 30 July 2024, in patients with HER2-positive MBC, median rwPFS and OS was 12.1 [95% confidence interval (CI): 8.5-14.7] and 22.7 months (95% CI: 16.6-28.8). The longer rwPFS, median 23.3 months, was observed in LOT 1-2, than 12.2 months in LOT 3-5 and 8.2 months in LOT≥6 (P=0.001). In patients with HER2-negative MBC, median rwPFS and OS was 7.7 (95% CI: 6.6-8.8) and 15.7 months (95% CI: 11.4-20.0). The median rwPFS for HR+ and HR- patients was 7.7 and 8.1 months, respectively (P=0.870). Longer rwPFS of 9.5 months was observed in LOT 1-4 compared to 6.4 months in LOT≥6 among HER2-negative patients (P=0.026). Patients with prior ADCs exposure showed significantly shorter rwPFS of T-DXd in both HER2-positive (P=0.032) and negative patients (P=0.039). Brain metastasis did not impact the effectiveness of T-DXd. Incidence of AEs of any grade was 69.3% and severe (grade 3 or above) AEs was 13.9%; no fatal AEs were observed. Interstitial lung disease (ILD) occurred in 23 patients (7.4%), with 15 (4.9%) of grade 1, 4 (1.3%) of grade 2, and 4 (1.3%) of grade 3. 80.7% of ILD patients, including all with grade 1 and one with grade 2, underwent a rechallenge with T-DXd after symptomatic treatments and careful evaluations.

Interpretation

In this largest dataset of T-DXd for Chinese patients with MBC to date, encouraging rwPFS of T-DXd was seen in heavily pretreated HER2-positive and HER2-negative MBC patients. Longer rwPFS was observed in MBC patients with fewer LOT and no prior ADC exposure. Meanwhile, T-DXd showed a manageable toxicity profile in understudied real-world patients. Rechallenge of T-DXd is feasible following effective symptomatic treatments and comprehensive assessments of ILD severity and recovery.

Funding

This work was supported by grants from Beijing Science and Technology Innovation Medical Development Foundation (KC2022-ZZ-0091-4).