KEY TAKEAWAYS
- The DESTINY-B12 phase III trial aimed to evaluate T-DXd efficacy in HER2-positive mBC ± BM.
- The primary endpoints were to determine PFS and ORR.
- T-DXd showed significant and durable clinical activity in patients with HER2+ mBC and ± BM.
Intracranial activity of trastuzumab deruxtecan (T-DXd) has been noted in small or retrospective patient cohorts with HER2-positive metastatic breast cancer (mBC) and brain metastases (BM), either stable or active (untreated/treated and progressing).
Nancy Lin and the team aimed to provide the most extensive prospective evaluation of T-DXd efficacy in patients with HER2-positive mBC and BM.
They performed an inclusive analysis on adults with HER2+ mBC who experienced progression on ≤2 prior lines of therapy in the metastatic setting. Patients were enrolled into either a BM cohort, which included those with stable or active (untreated/treated progressing) BM not requiring immediate local therapy or a non-BM cohort. Patients in the BM cohort were allowed to use dexamethasone (≤3 mg daily) or an equivalent for symptom control.
The study design did not permit cross-cohort comparison. Patients received T-DXd at a dose of 5.4 mg/kg intravenously every 3 weeks. The primary endpoints were progression-free survival (PFS) in the BM cohort and objective response rate (ORR) in the non-BM cohort, assessed per RECIST 1.1 by an independent central review.
Additional endpoints included CNS PFS, CNS ORR, ORR (BM cohort), and safety. Interstitial lung disease (ILD) and pneumonitis were reported by investigators, with no adjudication committee involved.
A total of 504 patients were treated (263 in the BM cohort and 241 in the non-BM cohort). A median follow-up of 15.4 (range: 0.1-30.0) months was observed for the BM cohort and 16.1 (0.8-28.4) months for the non-BM cohort.
The 12-month PFS for the BM cohort was 61.6% (95% CI: 54.9-67.6), and CNS PFS was 58.9% (95% CI: 51.9-65.3). This was similar in patients with stable (57.8% 95% CI 48.2, 66.1) and active (60.1% 95% CI 49.2, 69.4) BM. CNS ORR was 79.2% (95% CI: 70.2-88.3) in patients with stable BM and 62.3% (95% CI: 50.1-74.5) in patients with active BM.
Pneumonitis/ILD occurred in 16.0% of patients (n=42) with BM and 12.9% (n=31) among non-BM cohorts. Of these 5 ILD/pneumonitis events were reported as co-occurring with opportunistic infection (1.9% BM cohort).
The study concluded that T-DXd demonstrated significant and lasting overall and intracranial clinical activity in patients with HER2+ mBC, including those with stable or active BM, with no new safety concerns observed.
The trial was supported by AstraZeneca and Daiichi Sankyo.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/23
Clinical Trial: https://clinicaltrials.gov/study/NCT04739761
Lin N, Ciruelos EM, Jerusalem G, et al. (2024). “Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINYBreast-12 primary results.” Presented at ESMO-2024 (Abstract LBA18).
