SABCS 2019: Novel Antibody-Drug Conjugate in HER2-Positive Metastatic Breast Cancer
Posted: Monday, December 16, 2019
According to research simultaneously published in The New England Journal of Medicine and presented at the 2019 San Antonio Breast Cancer Symposium (Abstract GS1-03), the novel antibody-drug conjugate [fam-] trastuzumab deruxtecan (T-DXd) contributed to a significant clinical benefit in patients with HER2-positive breast cancer who had undergone considerable prior treatment.
“The high rate of durable responses observed with trastuzumab deruxtecan in patients whose cancers had progressed on T-DM1 and other therapies suggests this agent could provide a new treatment option for this patient population,” noted Ian E. Krop, MD, PhD, of Dana-Farber Cancer Institute, Boston, in an American Association for Cancer Research press release.
The two-part, phase II study, known as DESTINY-Breast01, enrolled 184 women with metastatic breast cancer who had previously undergone treatment with ado-trastuzumab emtansine (T-DM1). The median number of previous treatments was six, and 53% of patients had hormone receptor–positive disease. A total of 180 women had experienced disease progression during or after that treatment, and 4 had discontinued treatment for other reasons. All received 5.4 mg/kg of T-DXd—the dose recommended following pharmacokinetics in part 1 of the study—for a median duration of 6.9 months.
Comparable to results achieved in a prior phase I study, the objective response rate for patients receiving this dose was 60% (vs. 59%). A total of 6% of patients achieved a complete response, and 54.9% achieved a partial response. With a disease control rate of 97%, just five patients had anything other than stable disease at the initial post-baseline assessment, and participants experienced a median progression-free survival of 16.4 months.
Treatment-related adverse events were reported in almost all participants (99%), with 57% experiencing grade 3 or higher. The most common adverse events overall were gastrointestinal, including nausea and vomiting, and higher-grade adverse events included reduced neutrophil count and anemia. Treatment-related interstitial lung disease occurred in 25 patients, and although most cases were of a low grade, four grade 5–related deaths occurred.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.
