Around the Practice: Updates in Treating HER2+ Breast Cancer - Episode 1

HER2+ Breast Cancer Treatment Landscape and New Findings Presented at ESMO 2021

Sara A. Hurvitz, MD, briefly describes the treatment landscape for HER2+ breast cancer and the panelists take an in-depth look at the data from the DESTINY-Breast03 trial.

Sara Hurvitz, MD: Hello, I'm Dr Sara Hurvitz from the University of California, Los Angeles, and I’m a breast medical oncologist. Welcome to this CancerNetworkⓇ presentation "Around the Practice: Updates in Metastatic HER2+ Breast Cancer". I'm your host, and joining me today is Dr Neil Iyengar from Memorial Sloan Kettering Cancer Center, Dr Gadi Vijayakrishna from the University of Illinois Cancer Center in Chicago, and Dr Reshma Mahtani from the University of Miami.

Today, we're going to discuss recent data presented at ESMO [European Society for Medical Oncology] 2021 at the annual meeting, this occurred very recently, and we’ll talk about current challenges in the treatment of patients with HER2-postitive metastatic breast cancer. We'll review two patient cases, and we'll involve our audience by using an interactive online platform to answer several polling questions that will be discussed by our panelists. In our first segment, we're going to discuss HER2+ metastatic breast cancer and the updates from ESMO. We're going to discuss 5 abstracts that were presented at ESMO, and as we look at these abstracts we will put them into context and understand what the implications are for the community in academic practice. We’ll discuss whether these were practice-changing abstracts, how they will affect the treatment of your own patients, what outcomes you're looking for in terms of efficacy and toxicity, and how you educate your patients regarding the management of side effects. We know that HER2-postitive metastatic breast cancer is a rapidly evolving field right now. We have 8 FDA-approved therapies that target HER2with more to come. A new ADC [antibody-drug conjugate] was presented at ESMO, I'm excited to discuss how you are implementing the new data and what your standard of care is for HER2-postitive metastatic disease. Dr Iyengar, there was a big data splash LBA1, looking at the efficacy of T-DXd versus T-DM1[trastuzumab emtansine] in the DESTINY-Breast03 study, can you explain that?

Neil Iyengar, MD: This was big news from ESMO. To highlight the key points from this trial, DESTINY-Breast-03 was a randomized phase 3 trial testing trastuzumab deruxtecan versus trastuzumab emtansine or T-DM1 in patients with HER2-postitive metastatic breast cancer. The trial included a little over 500 patients, eligible patients had HER2-postitive unresectable or metastatic breast cancer and had previously been treated with trastuzumab plus a taxane in the metastatic setting. Patients with stable treated brain [metastases] were eligible for enrollment on this trial. Patients were randomized in a one-to-one fashion to either trastuzumab deruxtecan or T-DM1 and the primary endpoint was progression-free survival. Some important things about the study population to remember as we interpret the data, the median age was 54 years and the majority of patients, close to 60%, were enrolled in Asia. Nearly 50% of the patients were receiving study treatment in the second line and the rest were receiving study treatment in the third line or beyond. All patients had prior trastuzumab and about 60% enrolled had prior pertuzumab. This is progression-free survival with a follow-up of 15 months, median progression-free survival was not reached in the trastuzumab deruxtecan arm, but median PFS [progression-free survival] was 6.8 months in the T-DM1 arm. The 12-month PFS rate was 75% in the trastuzumab deruxtecan arm versus 34% in the T-DM1 arm and the hazard ratio was 0.28 favoring trastuzumab deruxtecan. There was an overall survival benefit reported with a hazard ratio of 0.56, and an objective response rate of 80% in the trastuzumab deruxtecan arm versus 34% in the T-DM1 arm. There were no new safety signals in terms of adverse events and the rate of any grade interstitial lung disease, which is important since the first single-arm phase 2 trial that was reported. The rate of ILD [interstitial lung disease] was 10.5% in the trastuzumab deruxtecan arm and there was no grade 4 or grade 5 ILD events. The ILD rate here was slightly better than what we saw earlier. Overall, this is impressive activity for trastuzumab deruxtecan confirming what was seen in the phase 2 trial and a reassuring safety profile specifically ILD, which was a slightly better. This data is important as we think about treatment options and specifically how we may sequence new treatment options for our patients.

Sara Hurvitz, MD: The data was exciting and I agree that PFS P value with the statistical significance 10 to the 22nd, I've never seen anything like it. The survival data, as you said, is very immature. We don't yet have statistical significance, but certainly quite reassuring.

This transcript has been edited for clarity.