Standard Treatment Approaches in HER2+ MBC

EP: 1.Global Trends in HER2+ MBC

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EP: 2.Standard Treatment Approaches in HER2+ MBC

EP: 3.Updated Data From DESTINY-Breast03 in HER2+ MBC

EP: 4.Subgroup Analyses of DESTINY-Breast03 in HER2+ MBC

EP: 5.Managing TRAEs Associated With Novel HER2+ MBC Therapies

EP: 6.T-DXd for HER2+ MBC and Interstitial Lung Disease

EP: 7.Novel Combination Approaches for HER2+ MBC

EP: 8.Updates to HER2CLIMB in HER2+ MBC

EP: 9.Updates in the Management of HER2+ MBC With Brain Metastases

EP: 10.ADCs Under Investigation for HER2+ MBC

EP: 11.Therapeutic Sequencing in HER2+ MBC

EP: 12.Optimizing Therapy in HER2+ MBC Across the Globe

EP: 13.Addressing Treatment Gaps in HER2+ MBC

Volkmar Müller, MD, Prof Dr: Now, we’ll discuss systemic therapy options for HER2-positive metastatic disease in your countries. What’s your standard of care in the first and second line, and which factors do you consider when choosing treatment?

Giuseppe Curigliano, MD, PhD: The first-line standard of care in Europe and in the United States is the combination of pertuzumab, trastuzumab and taxanes. We consider the treatment-free interval between the end of adjuvant treatment and the reappearance of the disease in the metastatic setting. According to the data of the CLEOPATRA trial that will be discussed later by Dr Traina, that interval should be at least 1 year. In the second-line setting, we have T-DM1 [trastuzumab emtansine] as the standard of care in my country, but we know from the DESTINY-Breast03 trial, which was presented during the ESMO [European Society for Medical Oncology] meeting, that we have a new standard of care, which we will discuss later. Finally, dual blockade and T-DM1 are still present as a standard of care in many guidelines across the world. In the third-line setting, if you did not receive T-DM1 in the second line, we have T-DM1, or the combination of lapatinib and capecitabine, or neratinib, or the potential use of tucatinib plus trastuzumab plus capecitabine. We can now explain why the guidelines are designed as I described, and Dr Traina will discuss the CLEOPATRA trial.

Tiffany A. Traina, MD: I completely agree, our standard of care in the first-line setting is combination taxane, trastuzumab, pertuzumab. The CLEOPATRA trial, now several years old, was nearly 1000 patients, first-line HER2+ metastatic breast cancer, with a randomization of docetaxel, trastuzumab to docetaxel, trastuzumab, pertuzumab. That study had remarkable efficacy, and now with over 8 years of follow-up, there was a 30% improvement in overall survival [OS] by the addition of pertuzumab to docetaxel and trastuzumab. That was a 16-month difference in overall survival with the addition of pertuzumab. There have been subsequent studies looking at paclitaxel with trastuzumab and pertuzumab. In the United States we use more weekly paclitaxel, which is supported by our guidelines as an option in the first-line setting.

Giuseppe Curigliano, MD, PhD: What about the EMILIA trial, can you remind us the inclusion criteria and the benefit in terms of PFS [progression-free survival] and overall survival?

Tiffany A. Traina, MD: The EMILIA trial sought to answer what was the optimal second-line treatment; this is almost 10 years ago. That trial required women to have had a prior taxane and trastuzumab. About 1000 patients were randomized to what was a reasonable standard of care at the time of capecitabine with lapatinib versus the antibody-drug conjugate T-DM1. That study showed a significant improvement in median progression-free survival of about 9.6 months versus 6.5 months, as well as an improvement in median overall survival. Median overall survival with T-DM1 was about 30 months versus 25 months. Based on high efficacy, PFS, OS, and a favorable toxicity profile, T-DM1 became a second-line standard of care for patients with HER2+ metastatic breast cancer.

Transcript edited for clarity.