FDA Workshop provides updates on new drugs for breast cancer


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3 minutes
Angela DeMichele, MD, MSCE
Angela DeMichele, MD, MSCE

The Food and Drug Administration’s Breakthrough Therapy Designation (BTD) pathway produced three new breast cancer treatments in 2020, including two antibody-drug conjugates.

“Antibody-drug conjugates are an important new drug class,” said Angela DeMichele, MD, MSCE, Jill & Alan Miller Endowed Chair in Breast Cancer Excellence, Professor of Medicine and Co-Leader of the Breast Cancer Center at the University of Pennsylvania Abramson Cancer Center. “These agents have specific features that adapt across breast cancer subtypes.”

Dr. DeMichele was joined by a panel of FDA scientists who discussed the new BTD agents during the “FDA and Breast Cancer Workshop” on Tuesday, Dec. 8.


Sacituzumab govitecan-hziy is the first antibody-drug conjugate approved for triple negative breast cancer (TNBC) said FDA pediatric oncologist Christy Osgood, MD. Early clinical data showed an overall response rate of 33% and a mean duration of response of 7.7 months. Both are significantly better than earlier third-line TNBC options eribulin and ixabepilone

Christy Osgood, MD
Christy Osgood, MD

The new agent links a humanized monoclonal antibody, sacituzumab, and SN-38, the active metabolite of irinotecan.

“The antibody binds to surface antigen trop-2 and delivers SN-38 to the cancer cell,” Dr. Osgood said. “SN-38 prevents the relegation of single strand topoisomerase-induced single strand breaks, ultimately resulting in apoptosis and cell death.”

Sacituzumab carries black box warnings for severe neutropenia and severe diarrhea. Women who are homozygous for UGT1A1*128 are at increased risk for neutropenia.  A confirmatory trial of Sacituzumab vs. physician’s choice of treatments is underway, Dr. Osgood continued.

Trastuzumab Deruxtecan

Trastuzumab deruxtecan (T-DXd) was approved for metastatic HER2+ breast cancer. The agent is a combination of trastuzumab and DXd, a topoisomerase I inhibitor derived from exatecan. 

T-DXd showed an objective response rate of 60% in early trials with 234 patients, reported FDA clinical reviewer Preeti Narayan, MD. The median duration of response was 14.8 months.

Nausea, fatigue, vomiting, and alopecia are the most common adverse events, she continued, but lung toxicity is the most worrisome.

Nine percent of patients developed ILD and 2.6% of patients died from ILD, prompting a black box warning.

“Lung toxicity is a very important safety signal for clinicians and patients to be aware of,” Dr. Narayan said. “It is essential to address any potential or suspected lung toxicity in a timely manner.”


Tucatinib is the first agent to be approved for HER2+ breast cancer with brain metastases. This tyrosine kinase inhibitor of HER2 was jointly evaluated and approved by FDA and regulatory authorities in Australia, Canada, Singapore, Switzerland, and the US.

About half of the patients in the HER2CLIMB trial had active or stable brain metastases, said FDA medical oncologist Mirat Shah, MD. Tucatinib agent showed progression-free survival of 7.6 months in patients with brain mets vs 5.4 months for placebo, a hazard ratio of 0.48. Results were similar in the overall study population.

About 80% of patients reported diarrhea, including two deaths. Mild-moderate transaminase elevation was common, but there were no instances of liver failure or death in these cases.

“Brain metastases are relatively common in patients with metastatic HER2+ breast cancer,” Dr. Shaw said. “Tucatinib is the first FDA approval to specify brain metastases in the indication statement.”

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