Trastuzumab Deruxtecan in Advanced HER2-Positive Gastric and Breast Cancers
Two phase I studies reported in The Lancet Oncology indicate activity of the antibody-drug conjugate trastuzumab deruxtecan in advanced HER2-positive gastric cancer and advanced HER2-positive breast cancer previously treated with trastuzumab emtansine (T-DM1). Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanized anti-HER2 antibody, cleavable peptide-based linker, and topoisomerase I inhibitor payload.
Gastric Cancer
As reported by Shitara et al, 44 patients from eight U.S. and six Japanese sites with advanced HER2-positive gastric or gastroesophageal junction cancer received at least one dose of trastuzumab deruxtecan at the recommended phase I expansion dose. An objective response was observed in 19 patients (43.2%). The median duration of response was 7.0 months.
The most common grade ≥ 3 adverse events included anemia (30%), decreased neutrophils (20%), decreased platelets (18%), and decreased white blood cells (6%). Serious adverse events occurred in 11 patients (25%). Three cases of grade 2 pneumonitis and one case of grade 3 pneumonitis occurred. No treatment-related deaths were reported.
The investigators concluded, “Trastuzumab deruxtecan had a manageable safety profile and showed preliminary activity in heavily pretreated patients with HER2-positive gastric or gastroesophageal junction cancer. These results support further investigation of trastuzumab deruxtecan for HER2-positive gastric or gastroesophageal junction cancer posttrastuzumab.”
Kohei Shitara, MD, of the National Cancer Center Hospital East, Kashiwa, Chiba, is the corresponding author for this report in The Lancet Oncology.
Breast Cancer
As reported by Tamura et al, 115 patients from eight U.S. sites and six Japanese sites with advanced HER2-positive breast cancer previously treated with T-DM1 received at least one dose of trastuzumab deruxtecan at the recommended phase I expansion dose. A confirmed objective response was observed in 66 (59.5%) of 111 evaluable patients. The median duration of response was 20.7 months.
Common grade ≥ 3 adverse events included anemia (17%), decreased neutrophils (4%), decreased white blood cells (9%), and decreased platelets (8%). Serious adverse events occurred in 19% of patients. There were 20 cases of interstitial lung disease, pneumonitis, or organizing pneumonia, with 1 case classified as grade 3 and two treatment-related deaths due to pneumonitis being observed.
The investigators concluded, “Trastuzumab deruxtecan had a manageable safety profile and showed preliminary activity in [T-DM1]-pretreated patients with HER2-positive breast cancer. These results suggest that further development in phase II and III clinical trials for HER2-positive breast cancer is warranted.”
Kenji Tamura, MD, National Cancer Center Hospital, Tokyo, is the corresponding author for the breast cancer study.
Disclosure: Both studies were funded by Daiichi Sankyo Co, Ltd. For full disclosures of the study authors, visit thelancet.com here and here.
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