KEY TAKEAWAYS
- The phase I trial aimed to assess safety, tolerability, and early effectiveness of T-DXd with standard ET in HER2-low, HR+ mBC.
- The primary endpoints were safety and tolerability.
- The safety profiles of T-DXd-ET combinations were generally comparable to T-DXd monotherapy, with manageable AEs through dose modification and routine clinical practice.
Trastuzumab deruxtecan(T-DXd) is globally approved for treating unresectable or metastatic HER2-low breast cancer (mBC) in adults with specific IHC scores, indicated for patients who received prior metastatic chemotherapy or experienced disease recurrence within 6 months after completing adjuvant chemotherapy.
Komal Jhaveri and her research team spearheaded the study that aimed to assess the safety, tolerability, and preliminary activity of T-DXd in combination with standard-of-care (SOC) therapies for patients with HER2-low hormone receptor-positive mBC, as part of the Phase 1b, multicenter, open-label study arms during the dose-expansion stage.
Eligible patients, with centrally confirmed HER2-low advanced/mBC and measurable disease per RECIST 1.1, documented as HR+, were enrolled. Patients, limited to 1 prior line of ET ± targeted therapy (excluding prior mBC chemotherapy), received T-DXd + anastrozole (T-DXd + ANA) or T-DXd + fulvestrant (T-DXd + FUL). Primary endpoints were safety and tolerability, with secondary endpoints including ORR, progression-free survival (PFS), duration of response (DoR) (evaluated by investigator per RECIST 1.1), and overall survival (OS). Data cutoff was approximately 24 weeks post-last patient’s study treatment.
About 21 patients received T-DXd + ANA, while 20 received T-DXd + FUL. Median ages were 55 and 66 years for the two arms, with 67% and 75% having prior ET ± targeted therapy for mBC. Additionally, 33% and 25% of patients had no prior line of treatment for mBC. The median follow-up in censored patients was 12.1 months (range 4.0,17.3) for the T-DXd + ANA arm and 8.5 months (range 1.3, 15.1) for the T-DXd + FUL arm.
Adverse events(AEs) occurred in 95.2% (20/21) of patients in the T-DXd + ANA arm and 100% (20/20) in the T-DXd + FUL arm, with AEs ≥Grade 3 in 47.6% (10/21) and 55.0% (11/20) in each arm, respectively. Any-grade AEs ≥30% included adjudicated drug-related interstitial lung disease/pneumonitis events (15%) in the T-DXd + FUL arm (all Grade 2; at DCO, one case had resolved, one was resolving, and one was not resolved). Confirmed ORR was 71.4% (15/21; 95% CI 47.8, 88.7) in the T-DXd + ANA arm, and 40.0% (8/20; 95% CI 19.1, 64.0) in the T-DXd + FUL arm. OS data was not mature at this DCO.
The results showed that combining T-DXd with hormone therapies (anastrozole or fulvestrant) showed similar safety to T-DXd alone and was effective in treating both first and second-line HER2-low, hormone receptor-positive metastatic breast cancer. This suggests a promising new option for these patients. The study is sponsored by AstraZeneca.
Source: https://atgproductions.net/atgclients/sabcs/2023_SABCS_Abstract_Report-12-1-23_Compressed.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT04556773
Jhaveri K, André F, Hamilton E, et al. (2023).’’Trastuzumab deruxtecan (T-DXd) in combination with anastrozole or fulvestrant in patients with HER2-low HR+ advanced/metastatic breast cancer: a Phase 1b, open-label, multicenter, dose-expansion study (DESTINY-Breast08).’’ Presented at SABCS 2023 (RF02-03).
