KEY TAKEAWAYS
- The DB-07 phase 1/2 trials aimed to evaluate the safety, tolerability, and antitumor activity of T-DXd ± pertuzumab as 1L treatment in people with HER2+ metastatic breast cancer.
- The primary endpoints were safety and tolerability.
- The study concluded that T-DXd and P show promising efficacy and safety; Phase 3 data is forthcoming.
Trastuzumab deruxtecan (T-DXd) is approved for adults with HER2+ advanced or metastatic breast cancer (mBC) who have previously received an anti-HER2-based regimen. The DESTINY-Breast07 study, a Phase 1b/2 multicenter, open-label, modular trial, explores the safety, tolerability, and antitumor activity of T-DXd alone or in combination with other anticancer agents (NCT04538742).
Fabrice Andre and the team aimed to assess T-DXd ± pertuzumab as a first-line treatment for HER2+ metastatic breast cancer.
Patients had locally assessed HER2+ mBC with measurable disease and no or stable brain metastases. A disease-free interval of at least 12 months from (neo)adjuvant therapy was required, and no prior therapy for mBC was allowed. Participants were stratified by hormone receptor status, disease status (recurrent vs. de novo), and PD-L1 expression. They received T-DXd 5.4 mg/kg intravenously every three weeks (Q3W) as monotherapy or in combination with pertuzumab (P) 420 mg IV Q3W, with an initial loading dose of 840 mg.
The primary endpoints were safety and tolerability, while key secondary endpoints included objective response rate (ORR) and progression-free survival (PFS), as determined by RECIST 1.1 criteria assessed by investigators.
The results revealed that 75 participants were treated in the T-DXd module and 50 in the T-DXd + P module, with median follow-ups of 19.2 months (range 8.7–29.2) and 20.6 months (range 13.3–26.7), respectively. The median age was 57 years in both modules. As of August 1, 2023, the most common adverse event (AE) was nausea (T-DXd, 70.7% [4.0% Grade 3]; T-DXd + P, 68.0% [0% Grade 3]).
Diarrhea was reported in 34.7% (2.7% Grade 3) and 60.0% (6.0% Grade 3) of participants in the T-DXd and T-DXd + P modules, respectively. No Grade ≥4 nausea or diarrhea events occurred. Adjudicated drug-related interstitial lung disease (ILD) or pneumonitis was reported in 6 (8.0%) and five (10.0%) participants in the T-DXd and T-DXd + P modules, respectively (all Grade ≤2).
Only 1 non-treatment-related AE resulting in death was reported in the T-DXd module (post-acute COVID-19 syndrome); none were reported in the T-DXd + P module. The confirmed objective response rate (ORR) was 77.3% (80% CI 70.0, 83.6) with T-DXd and 82.0% (80% CI 73.1, 88.8) with T-DXd + P. The PFS rate at 12 months was 77.3% (80% CI 69.0, 83.7) with T-DXd and 89.4% (80% CI 81.9, 93.9) with T-DXd + P.
The study concluded that the safety profiles were consistent with known profiles for T-DXd and P, with no Grade ≥3 ILD events. Early data showed promising efficacy in both modules. The DESTINY-Breast07 study is ongoing; analyses from the Phase 3 DESTINY-Breast09 clinical trial will provide definitive data on T-DXd ± P in first-line HER2+ metastatic breast cancer.
The trial was sponsored by AstraZeneca.
Source: https://meetings.asco.org/abstracts-presentations/233642
Clinical Trial: https://clinicaltrials.gov/study/NCT04538742
Andre F, Hamilton EP, Loi S, et al.(2024). “DESTINY-Breast07: Dose-expansion interim analysis of T-DXd monotherapy and T-DXd + pertuzumab in patients with previously untreated HER2+ mBC.” Presented at ASCO 2024. J Clin Oncol 42, 2024 (suppl 16; abstr 1009). DOI: 10.1200/JCO.2024.42.16_suppl.1009 (1009)
