Phase II study of cabazitaxel as second-line treatment in patients with HER-2 negative metastatic breast cancer previously treated with taxanes.

1089 Background: Cabazitaxel is a new taxoid efficient in stabilizing microtubules against depolymerization. Preclinical and limited clinical data indicate that cabazitaxel might be effective in breast cancer patients resistant to first-generation taxanes. Methods: The purpose of the current multicenter phase II trial was to evaluate the activity and safety of cabazitaxel as 2nd-line treatment, given on day 1 of a 21-day cycle, in patients with HER-2 negative metastatic breast cancer (mBC), previously treated with taxanes. Prophylaxis with G-CSF was recommended to all patients. The primary endpoint was the objective response rate (ORR), while secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response (DOR) and the safety profile. Results: Eighty-four patients were enrolled between 2012 and 2016. Among them, 3 patients (3.6%) were ineligible but received at least two cycles of treatment. In total, 499 cycles of cabazitaxel were administered (median 4; range 1-39). Median relative dose intensity was 0.99 (range 0.79-1.49). Seven patients were not evaluated for tumor response. In the 77 patients with evaluable treatment response, the ORR was 24.7% (1 complete and 18 partial responses). The disease-control rate was 58.4%, while the median DOR was 5.6 months (range 0.7-51.3). Within a median follow-up of 32.2 months, the median PFS was 3.7 months (95% CI 2.23-4.36), whereas the median OS was 15.2 months (95% CI 11.21-21.54). Regarding toxicity, grades 3-4 neutropenia and febrile neutropenia were reported in 22.6% and 6.0% of patients, respectively. Two fatal events were reported (1 febrile neutropenia; 1 sepsis) related to study treatment. Most frequent non-hematological events were fatigue, diarrhea, nausea (grade 1-3). There were no unexpected serious AE, and no new safety signal was revealed. Conclusions: This phase II trial suggests that cabazitaxel is active (disease control rate of almost 60%) with a manageable toxicity profile as 2nd-line treatment in taxane-pretreated patients with HER-2 negative mBC. Clinical trial information: NCT01693549.