The primary endpoint of objective response rate (ORR), confirmed by independent central review, was 60.9% with trastuzumab deruxtecan monotherapy (5.4mg/kg). Patients had a median of six prior therapies for metastatic disease (2-27).
Patients achieved a disease control rate (DCR) of 97.3% with a median duration of response (DoR) of 14.8 months and median progression-free survival (PFS) of 16.4 months. The median overall survival (OS) has not yet been reached, with an estimated survival rate of 86% at one year. The results were consistent across subgroups of patients.
José Baselga, Executive Vice President, Oncology R&D, said: “The clinically meaningful and durable responses seen among these patients illustrate the potential of trastuzumab deruxtecan to establish a new standard of care. These results are impressive, as women with this advanced stage of breast cancer have already endured multiple prior therapies for HER2-positive metastatic breast cancer.”
Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: “The strength of the pivotal results and the consistency with previously reported trastuzumab deruxtecan data further underscore that this specifically engineered HER2-targeted antibody drug conjugate is delivering on its intent of enhancing efficacy for patients with HER2-positive metastatic breast cancer.”
Ian E. Krop, a principal investigator of the DESTINY-Breast01 trial and Associate Chief, Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, said: “These results are particularly striking as trastuzumab deruxtecan prompted a high level of durable tumour reduction among patients, the majority of whom had exhausted most if not all standard therapies for HER2-metastatic breast cancer. We are excited by these results and their potential to help patients with this advanced stage of breast cancer.”
The data were included as part of the press programme at the 2019 San Antonio Breast Cancer Symposium and simultaneously published online in The New England Journal of Medicine.
Prior therapies included trastuzumab emtansine (100%), trastuzumab (100%), pertuzumab (65.8%), other anti-HER2 therapies (54.3%), hormone therapies (48.9%) and other systemic therapies (99.5%). Median treatment duration for trastuzumab deruxtecan was 10 months (0.7-20.5) with a median duration of follow-up of 11.1 months (0.7-19.9). As of data cut-off on 1 August 2019, 42.9% of patients remained on treatment.
The safety and tolerability profile of trastuzumab deruxtecan in DESTINY-Breast01 was consistent with that observed in the Phase I trial. The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count (20.7%), anaemia (8.7%), nausea (7.6%), decreased white cell count (6.5%), decreased lymphocyte count (6.5%) and fatigue (6.0%). Overall, 13.6% of patients had confirmed interstitial lung disease (ILD) related to treatment as determined by an independent review. The events were primarily Grade 1 or 2 (10.9%) in severity with one Grade 3 (0.5%) and no Grade 4 events. Four deaths (2.2%) were determined to be due to ILD.
Regulatory submission of trastuzumab deruxtecan for the treatment of patients with HER2-positive metastatic breast cancer was recently accepted with Priority Review by the US Food and Drug Administration. A regulatory submission has also been made to Japan’s Ministry of Health, Labour and Welfare.
Source: Company Press Release