HER2+ BC: A Year in Review and Updates from SABCS - Episode 1

2020 in Review: HER2+ Breast Cancer

Experts in breast oncology discuss the evolving landscape in early stage and metastatic HER2-positive breast cancer.

Hatem Soliman, MD: This is a review of the recent updates on early and advanced breast cancer from this past year. There are exciting new data from the 2020 San Antonio Breast Cancer Symposium. I am Dr. Hatem Soliman, medical oncologist specializing in breast cancer, and also experimental therapeutics in the Center for Women’s Oncology in the breast department at Moffit Cancer Center in Tampa, Florida.

Andrew Seidman, MD: Just as things started getting dark around the world with this virus [coronavirus disease 2019], things started to get bright for women with HER2-positive breast cancer. In terms of neoadjuvant therapy, we now know we can tailor what happens post-operatively based on the results of pre-operative therapies. The use of trastuzumab emtansine in the adjuvant setting, based on the KATHERINE data, for patients not achieving a CR [complete response], has changed management. We’re beginning to see adaptive approaches to potentially think about de-escalation in the neoadjuvant setting. For the vast majority of patients who warrant the use of neoadjuvant therapy, we are guided by that prior approval of pertuzumab in combination with chemotherapy and trastuzumab as still the gold standard.

Hatem Soliman, MD: There’s been a shift in the paradigm for early stage disease, and it doesn’t appear to be getting any simpler as time goes on. There has been an embarrassment of riches in HER2+ metastatic breast cancer as well, with a slew of novel agents with activity that have been recently approved through the FDA.

Andrew Seidman, MD: There has been an accelerated, or conditional approval of trastuzumab deruxtecan, the antibody conjugate, where SN-38 is the cytotoxic payload and trastuzumab is the antibody. Shanu Modi, [MD,] as published in The New England Journal of Medicine, reported on very impressive activity for this antibody-drug conjugate with a response rate of 61%. In this paper, there was a median response rate of 14.8 months, and a median PFS [progression-free survival] of 16.4 months, which updated at San Antonio, are even more robust: a median duration of response of about 21 months, and a median PFS of 19.4 months.

We do need to be aware of the potential for interstitial lung disease with this agent, particularly in the midst of a viral pandemic. But this is one important new agent, and we’re all awaiting the results of the DESTINY-Breast02 trial, which will compare that to the treatment of physician’s choice, in that same setting. The HER2CLIMB study is leading to the full approval of tucatinib with trastuzumab and capecitabine, based on both PFS and OS [overall survival] benefits, including patients who have brain metastasis at baseline. We have a more targeted HER2 tyrosine kinase inhibitor with fewer off-target toxicities, such as gastrointestinal toxicities.

Also, the NALA study is showing the superiority of capecitabine and neratinib, a more promiscuous HER family kinase inhibitor, over capecitabine and lapatinib, with a PFS benefit and CNS [central nervous system] activity.

Transcript edited for clarity.