Douglas K. Marks, MD, clinical instructor, Department of Medicine, Perlmutter Cancer Center, NYU Langone Health, discusses investigational antibody—drug conjugates (ADCs) in HER2-positive breast cancer.

Ado-trastuzumab emtansine (T-DM1; Kadcyla) is approved for use in patients with HER2-positive breast cancer. The ADC has shown clinical benefit in the early-stage and metastatic settings, says Marks. Several additional ADCs have also shown potential, and are now being evaluated in phase III clinical trials. One such compound is [fam-] trastuzumab deruxtecan (DS-8201), which is being evaluated in the phase III DESTINY trials. Notably, the drug has shown activity in 

-amplified breast cancers. Although patients may experience chemotherapy-related adverse events, such as neutropenia and fatigue, the severity is less than one would expect with traditional cytotoxic chemotherapy, explains Marks. 

[Vic-]trastuzumab duocarmazine (SYD985) is a similar compound with a HER2-directed antibody and another payload. The drug also appears promising and is being investigated in the phase III TULIP trials.

Videos

Douglas K. Marks, MD, discusses investigational antibody–drug conjugates in HER2-positive breast cancer.

Dr. Marks on Investigational Antibody-Drug Conjugates in HER2+ Breast Cancer

Douglas K. Marks, MD, clinical instructor, Department of Medicine, Perlmutter Cancer Center, NYU Langone Health, discusses data from a small subset of patients with HER2-positive breast cancer enrolled in the PHENIX trial, which was presented at the 2019 ASCO Annual Meeting.

In the PHENIX study, researchers looked at pyrotinib combined with capecitabine (Xeloda) versus capecitabine alone; results showed that there was a significant improvement in progression-free survival and response rate in the pyrotinib/capecitabine arm, explains Marks.

Although the data was compelling, especially for patients with brain metastases, according to Marks, the study design is unlike other trials. The comparator arm did not include a HER2-directed therapy; rather, it explored capecitabine alone, which is atypical.

Douglas K. Marks, MD, discusses data from a small subset of patients with HER2-positive breast cancer enrolled in the PHENIX trial, which was presented at the 2019 ASCO Annual Meeting.

Dr. Marks on PHENIX Trial Data in HER2+ Breast Cancer

Douglas K. Marks, MD, clinical instructor, Department of Medicine, Perlmutter Cancer Center, NYU Langone Health, discusses the role of TKIs in HER2-positive breast cancer.

TKIs have taken a backseat to HER2-directed antibodies over the past few years. This is due, in part, to the fact that lapatinib (Tykerb) and neratinib (Nerlynx) were found to be inferior to other agents that were developed around the same time, like pertuzumab (Perjeta) and ado-trastuzumab emtansine (T-DM1; Kadcyla). However, these agents have re-emerged after demonstrating impressive central nervous system activity (CNS), says Marks.

For example, the irreversible pan-ErbB inhibitor pyrotinib demonstrated potent CNS activity in a phase II study published in the 

. In the trial, combining the agent with capecitabine led to a 64% reduction in the risk of disease progression or death compared with lapatinib plus capecitabine in Chinese patients with relapsed or metastatic HER2-positive breast cancer. Tucatinib is another TKI that has shown promise and is currently being evaluated in the ongoing phase II HER2CLIMB trial.

Douglas K. Marks, MD

Articles

Dr. Marks on Investigational Antibody-Drug Conjugates in HER2+ Breast Cancer

Dr. Marks on PHENIX Trial Data in HER2+ Breast Cancer

Dr. Marks on the Role of TKIs in HER2-Positive Breast Cancer