In a Japanese phase II trial (STATICE) reported in the Journal of Clinical Oncology, Nishikawa et al found that fam-trastuzumab deruxtecan-nxki (T-DXd) showed activity in patients with HER2-expressing advanced or recurrent uterine carcinosarcoma.
Study Details
In the multicenter trial, 32 evaluable patients with HER2 immunohistochemistry (IHC) scores ≥ 1 previously treated with chemotherapy were enrolled between December 2017 and June 2020. They received T-DXd at 6.4 or 5.4 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. The dose was amended to 5.4 mg/kg based on the updated recommended phase II dose for breast cancer.
Patients were assigned to a HER2-high group (IHC score ≥ 2+, n = 22; 9 received 6.4 mg/kg and 13 received 5.6 mg/kg) and a HER2-low group (IHC score =1+, n = 10; 5 each at the two dose levels). The primary endpoint was objective response rate on central review in the HER2-high group.
Responses
Median follow-up was 13.5 months (range = 4.0–33.0 months). In the HER2-high group, objective responses, including a complete response, were observed in 12 (54.5%, 95% confidence interval [CI] = 32.2%–75.6%) of 32 patients, including 8 (61.5%) of 13 receiving 5.4 mg/kg and 4 (44.4%) of 9 receiving 6.4 mg/kg. Median response duration was 6.9 months (95% CI = 4.1–12.6 months). Median progression-free survival was 6.2 months (95% CI = 4.0–8.8 months). Median overall survival was 13.3 months (95% CI = 8.8 months to not reached).
KEY POINTS
- Objective response was observed in 54.5% of patients in the HER2-high group.
- Objective response was observed in 70.0% of the HER2-low group.
In the HER2-low group, objective responses on central review (all partial) were observed in 7 (70.0%, 95% CI = 34.8%–93.3%) of 10 patients, including 3 (60%) of 5 receiving 5.4 mg/kg and 4 (80%) of 5 receiving 6.4 mg/kg. Median duration of response was 8.1 months (95% CI = 2.8 months to not reached). Median progression-free survival was 6.7 months (95% CI = 2.6–13.8 months). Median overall survival was not reached (95% CI = 9.8 months to not reached).
On investigator assessment, objective response rates were 68.2% in the HER2-high group and 60.0% in the HER2-low group.
Adverse Events
In the safety population of 33 patients, grade ≥ 3 adverse events occurred in 20 patients (61%), most commonly decreased neutrophils (27%), anemia (24%), decreased lymphocytes (21%), and hypoalbuminemia (12%). Grade ≥ 3 adverse events occurred in 93% of patients receiving an initial dose of 6.4 mg/kg vs 37% of those receiving an initial doe of 5.4 mg/kg.
Adverse events led to discontinuation of treatment in 11 patients (33%); the most commonly reported adverse events were pneumonitis/interstitial lung disease (ILD) in 6 (18%) and malaise in 2 (6%). Pneumonitis/ILD occurred in nine patients (27%) and was grade 1 or 2 in eight and grade 3 in one. No adverse events led to death.
The investigators concluded, “[T-DXd] has efficacy in patients with uterine carcinosarcoma, regardless of HER2 status. The safety profile was generally consistent with that previously reported. Toxicities were manageable with appropriate monitoring and treatment.”
Kan Yonemori, MD, PhD, of the Department of Medical Oncology, National Cancer Center Hospital, Tokyo, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Japan Agency for Medical Research and Development and Daiichi Sankyo Co, Ltd. For full disclosures of the study authors, visit ascopubs.org.
