Celgene Corporation (CELG) today announced that the results of its randomized phase II tnAcity trial of ABRAXANE® for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) will be presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) December 6-10, 2016. The trial found that an investigational weekly combination regimen of ABRAXANE + carboplatin had significantly longer progression-free survival (PFS) (7.4 months) compared to weekly regimens of either ABRAXANE + gemcitabine (5.4 months) or of carboplatin + gemcitabine (6.0 months) as first-line treatment of patients with metastatic triple-negative breast cancer (mTNBC).i
The phase II trial randomized 191 women with mTNBC to receive one of three weekly regimens (dosed 2 out of 3 weeks): ABRAXANE + carboplatin, ABRAXANE + gemcitabine, or carboplatin + gemcitabine as first-line treatment. The study findings demonstrated that ABRAXANE + carboplatin resulted in significantly longer PFS (7.4 months) than combination regimens with ABRAXANE + gemcitabine (5.4 months; P=0.02, HR 0.60 (95% CI, 0.39-0.93)) or carboplatin + gemcitabine (6.0 months; P= 0.03, HR 0.61 (95% CI, 0.39-0.94)). tnAcity also found that those treated with the ABRAXANE + carboplatin regimen experienced a longer median treatment duration (25 weeks) than those treated with ABRAXANE + gemcitabine (18.1 weeks) or carboplatin + gemcitabine (20.1 weeks).i
The most common grade ≥3 treatment emergent adverse events (TEAEs) observed in the ABRAXANE + carboplatin, ABRAXANE + gemcitabine, and carboplatin + gemcitabine arms, respectively, during the study were mainly hematologic and included neutropenia (42%, 27%, 52%), anemia (13%, 12%, 27%), thrombocytopenia (9%, 7%, 28%), leukopenia (6%, 3%, 11%), febrile neutropenia (5%, 2%, 0%), peripheral neuropathy (5%, 7%, 2%) and fatigue (3%, 15%, 3%). A median of 8 treatment cycles were initiated for the ABRAXANE + carboplatin arm and 6 cycles for both the ABRAXANE + gemcitabine and carboplatin + gemcitabine arms. The percentage of patients that discontinued any study drug due to a TEAE was 45% for ABRAXANE + carboplatin and 25% for each of the other arms. The most common AEs leading to discontinuation of any study drug included thrombocytopenia, anemia, neutropenia and drug hypersensitivity.i
“Metastatic triple negative breast cancer is one of the most challenging types of cancers for treating physicians and patients alike, and there remains an important unmet need in these patients to find more effective treatment options,” said Dr. Denise A. Yardley, Senior Investigator, Breast Cancer Research Program; Principal Investigator, Sarah Canon Research Institute. “These data add to the body of knowledge about ABRAXANE in metastatic triple negative breast cancer, a disease that requires additional research.”
After taking into consideration the rapidly changing breast cancer treatment landscape, which has a significant focus on immuno-oncology treatments, Celgene had determined not to move forward with the phase III portion of tnAcity. The Company will instead focus its breast cancer research support on ABRAXANE/Immunotherapy combinations and remains committed to applying the findings of tnAcity to ongoing and future research of ABRAXANE in breast cancer for patients with high unmet needs.
“The findings of tnAcity are encouraging, illustrating that an ABRAXANE-containing regimen may have activity in a type of breast cancer with few viable treatments and these findings give researchers additional insight into how to treat metastatic triple negative breast cancer,” said Michael Pehl, President, Hematology and Oncology for Celgene. “Celgene is committed to continuing to support research in breast cancer to identify regimens for patients with aggressive disease and in areas with limited treatment options.”
ABRAXANE is not indicated for the first-line treatment of metastatic breast cancer, or for the treatment regimens studied in tnAcity.
tnAcity is a phase II/III multicenter, open-label, randomized clinical trial conducted in 139 centers in 12 countries. The study evaluated the safety and efficacy of the investigational use of a weekly treatment regimen of ABRAXANE in combination with carboplatin or gemcitabine as a first-line treatment of women with metastatic triple negative breast cancer (mTNBC) compared to a gemcitabine + carboplatin regimen.ii