Trastuzumab deruxtecan (T-DXd) demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) benefit among patients with HER2-low metastatic breast cancer, when compared with chemotherapy.

These results were first presented by Giuseppe Curigliano, MD, University of Milan and European Institute of Oncology, Milan, Italy, at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting in Chicago, Illinois.

The multicenter, open-label, phase 3 DESTINY-Breast06 enrolled 866 patients with HER2-low (n = 713) or -ultralow (n = 153), hormone receptor (HR)-positive metastatic breast cancer who progressed on endocrine-based therapy, who had not received any prior chemotherapy for metastatic breast cancer. HER2-low is defined as IHC 1+ or 2+ with ISH-negative; HER2-ultralow is defined as IHC 0 with membrane staining. Patients were randomized on a 1-to-1 basis to receive either 5.4 mg/kg of trastuzumab deruxtecan, or physician’s choice of chemotherapy. The primary end point was PFS by blinded independent central review in the HER2-low population. Key secondary end points included PFS in the intent-to-treat population (including both HER2-low and -ultra patients) and overall survival (OS), while other end points were objective response rate (ORR) and safety.

The median PFS of HER2-low patients in the trastuzumab deruxtecan arm (n = 359) was 13.2 months vs 8.1 months for HER2-low patients in the chemotherapy arm (n = 354). This represents a significant improvement of PFS with trastuzumab deruxtecan vs chemotherapy (hazard ratio [HR], 0.62; P < .0001). The PFS results in the intent-to-treat and HER2-ultralow cohorts were consistent with the HER2-low results. At the time of this first interim analysis, OS results were immature. The confirmed ORR was 57.3% in the trastuzumab deruxtecan arm vs 31.2% in the chemotherapy arm, among the intent-to-treat population.

There were grade ≥3 drug-related adverse events reported in 10.6% of patients in the trastuzumab deruxtecan arm vs 31.4% in the chemotherapy arm. Adjudicated interstitial lung disease/pneumonitis occurred in 49 (11.3%; grade 3/4, 0.7%; grade 5, 0.7%) patients and 1 (grade 2, 0.2%) patients, respectively.

Dr Curigliano et al concluded, “DESTINY-Breast06 establishes trastuzumab deruxtecan as an effective new treatment option for patients with HR-positive, HER2-low and HER2-ultralow metastatic breast cancer, following 1 line or more of endocrine-based therapy and no prior chemotherapy.”

Ian Krop, MD, PhD, Yale Cancer Center, New Haven, Connecticut, added in his discussion that, for this patient population, “T-DXd is associated with greated efficacy than chemotherapy and potentially can be considered a new standard of care for these patients in either first or second line,” while noting, “improved HER2 testing assays are needed to distinguish HER2-low and -ultralow cancers from HER2-zero cancers, or we need to prove that testing is not clinically needed.” Dr Krop concluded, “The use of T-DXd in HR-negative, HER2-ultralow cancers should be evaluated, based on the very promising data we saw today…in HR-positive patients.”

Source:

Curigliano G, Hu X, Dent RA, et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). Presented at 2024 ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. Abstract #LBA1000.

Krop IE. Discussion of LBA1000. Presented at 2024 ASCO Annual Meeting. May 31-June4, 2024; Chicago, IL.