This study evaluated the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamate, in patients with HER2-negative, metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy. Although CT-2103 had activity in this small study, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected, and led to early termination of the trial.
Purpose: To evaluate the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamate, in patients with metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy.
Patients and methods: Eighteen women with HER2-negative breast cancer were enrolled. Patients received intravenous CT-2103 at a dose of 175 mg/m2 of conjugated paclitaxel over 10 min every 3 weeks, without routine premedication. Eighty-three percent of women had received prior chemotherapy as part of adjuvant (39%), metastatic (17%), or both adjuvant and metastatic (28%) treatment. Three patients (17%) had previously received a taxane in the adjuvant setting.
Results: Objective responses were observed in 4 of 18 patients (overall response rate, 22%, 95% confidence interval, 6 to 48%). Grade 3 or 4 neuropathy was observed in four patients. Grade 3 or 4 hypersensitivity reactions (HSR) were observed in four patients; none occurred prior to cycle 4 of therapy. Because of the higher-than-expected rate of HSR, the study was terminated early.
Conclusion: Although CT-2103 had activity in this small study of women with HER2-negative metastatic breast cancer, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected. Hypersensitivity reactions were most likely to occur in later cycles of treatment, suggesting a true drug allergy, distinct from the HSR typically seen with standard paclitaxel.