Trastuzumab deruxtecan superior to physician’s choice treatment in patients with metastatic HER2-positive breast cancer

1. Progression-free survival was greater in the trastuzumab group compared to standard care (17.8 months vs. 6.9 months).

2. Drug-related interstitial lung disease was more common with patients receiving trastuzumab deruxtecan.

Evidence Rating Level: 1 (Excellent)

Study Rundown: A large proportion of breast cancers are characterized by overexpression of HER2 receptors. While first-line therapy for HER2-positive breast cancer includes monoclonal antibodies such as trastuzumab, a large proportion of patients continue to show disease progression. This randomized controlled trial aimed to compare the safety and efficacy of trastuzumab deruxtecan with physician’s choice treatment (either capecitabine plus trastuzumab or capecitabine plus lapatinib) in patients with HER2-positive metastatic breast cancer. The primary outcome was progression-free survival while key secondary outcomes included overall survival and objective response rates. According to study results, patients in the trastuzumab deruxtecan group demonstrated significantly improved progression-free survival than those in physician’s choice treatment group. This study was strengthened by a randomized design with individuals from multiple countries, thus adding to its generalizability.

Click to read the study in The Lancet

Relevant Reading: Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer

In-depth [randomized-controlled trial]: Between Sept 6, 2018, and Dec 31, 2020, 816 patients were screened for eligibility across 227 clinical sites in North America, Europe, Asia, Australia, Brazil, Israel, and Turkey. Included were patients ≥ 18 years with HER2-positive unresectable or metastatic breast cancer, previous trastuzumab-emtansine therapy, an ECOG score of 0-1, and disease progression. Altogether, 608 patients (406 in trastuzumab and 202 in physician’s choice treatment) were included in the final analysis. The primary outcome of progression-free survival was significantly greater in the trastuzumab group (17.8 months) versus the physician’s choice treatment group (6.9 months; hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.28-0.45, p<0.0001). The majority of adverse events were mild-to-moderate in nature and comparable between both groups (53% in trastuzumab vs. 44% in physician’s choice treatment). However, drug-related interstitial lung disease was more common with trastuzumab deruxtecan (10%) versus physician’s choice of therapy (1%). Overall, findings from this study suggest that trastuzumab may be both safe and effective for the treatment of metastatic breast cancer.

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