A DESTINY-Breast09 (DB-)09 analysis of trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for patients (pts) with HER2+ advanced/metastatic breast cancer (a/mBC) and baseline (BL) brain metastases (BMs)

DESTINY-Breast09

Patient / Population Intervention / Exposure Comparison Outcome

In patients with HER2-positive advanced breast cancer and baseline brain metastases, trastuzumab deruxtecan plus pertuzumab prolonged CNS progression-free survival compared with taxane, trastuzumab and pertuzumab.

N

61patients

Design

Exploratory CNS efficacy analysis of the randomised DESTINY-Breast09 trial (NCT04784715) in patients with HER2-positive advanced or metastatic breast cancer, no prior systemic therapy for advanced disease and clinically inactive or treated and stable baseline brain metastases by blinded independent central review with at least one post-baseline brain scan, comparing trastuzumab deruxtecan plus pertuzumab (n=31) vs taxane, trastuzumab and pertuzumab (n=30).

Endpoint

Exploratory outcomes in patients with baseline brain metastases: CNS progression-free survival, progression-free survival, CNS confirmed objective response rate (complete plus partial response in brain) and CNS duration of response, all assessed by blinded independent central review per RECIST 1.1.

ResultMedian CNS progression-free survival with trastuzumab deruxtecan plus pertuzumab NE (95% CI 19.1-NE) vs 9.7 months (95% CI 4.2-19.2) with THP, HR 0.26 (95% CI 0.11-0.57). CNS-PFS events occurred in 9 (29.0%) vs 17 (56.7%). Median PFS 36.5 vs 11.1 months. CNS confirmed objective response rate 51.6% (95% CI 33.1-69.8) vs 26.7% (95% CI 12.3-45.9), with CNS complete response in 11 (35.5%) vs 7 (23.3%). Median CNS duration of response NE (95% CI 14.3-NE) vs 18.5 months (95% CI 8.3-NE). Median follow-up 23.6 months (range 2.8-41.4).

Manich CS, Loibl S, Jiang Z, et al. Presented at ESMO Congress 2026, abstract LBA49, 26 October. Not yet published.

Discussion & critique

In this exploratory analysis, trastuzumab deruxtecan plus pertuzumab gave a higher intracranial response rate and a lower hazard of CNS progression than THP in patients with baseline brain metastases. The analysis covers only 61 patients selected for having at least one post-baseline brain scan, so it does not keep the full protection of randomisation, and the abstract reports no P values. The data come from an interim cutoff: median CNS-PFS was not reached in the experimental arm, the confidence intervals are wide, and the abstract gives no overall survival or safety data for this subgroup. Only patients with clinically inactive or treated and stable brain metastases were eligible, so the results do not apply to active brain metastases. The abstract does not state whether treatment was blinded.