Pegram Unpacks Pivotal Data in Breast Cancer

Welcome to a very special edition of OncLive^® On Air! I’m your host today, Caroline Seymour.

OncLive^® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Mark D. Pegram, MD, to discuss the significance of the phase 2 DESTINY-Breast01 trial with fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive breast cancer and other compelling data sets from the 2020 ASCO Virtual Scientific Program and 2020 ESMO Breast Cancer Virtual Meeting.

In December 2019, the FDA granted an accelerated approval to the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received at least 2 prior anti–HER2-based regimens in the metastatic setting.

The approval is based on findings from the phase DESTINY-Breast01 trial. In the study, trastuzumab deruxtecan led to a confirmed objective response rate (ORR) of 60.9% and a median progression-free survival (PFS) of 16.4 months in this patient population.

The median duration of response was 14.8 months. Moreover, the drug was associated with improved ORR and PFS across multiple subgroups, irrespective of ECOG performance status, HER2 immunohistochemistry status, prior pertuzumab (Perjeta), time since disease diagnosis, and hepatic impairment at baseline.

Updated data indicated that the agent is also effective in patients who had stable, treated brain metastases. A total of 8 patients with brain metastases experienced an ORR of 58.3% and a median PFS of 18.1 months.

Common adverse effects consisted of gastrointestinal and hematologic toxicities. Interstitial lung disease (ILD) was identified in 13.6% of patients, and were grade 1/2 in 10.9% of patients, grade 3/4 in 0.5% of patients, and grade 5 in 2.2% of patients. Four deaths were reported and were attributed to ILD by independent adjudication; they were initially reported as respiratory failure, acute respiratory failure, lymphangitis, and pneumonitis in 1 patient each by the treating investigators.

In our exclusive interview, Dr. Pegram, Susy Yuan-Huey Hung Professor, co-director of Stanford’s Molecular Therapeutics Program, and director of the Breast Cancer Oncology Program, at Stanford Women's Cancer Center, discussed the unique structure of trastuzumab deruxtecan, initial and subset analyses from the DESTINY-Breast01 trial, potential adverse effects, and recommended management strategies for the agent.

Additionally, Dr. Pegram, spotlighted other notable data in breast cancer that were presented during the 2020 ASCO and ESMO Breast virtual meetings.