Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m(2) intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m(2) for ≤ 12 cycles. The primary endpoint was overall response rate (≥ partial response). Secondary endpoints included clinical benefit response rate (≥ minimal response), duration of response, progression-free survival, overall survival, and safety. A total of 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. Overall response rate was % with median duration of response of months. Median overall survival was months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirty-three patients (%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (%) withdrew because of an AE. Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. This trial was registered at as # NCT00511238 .
The data reviewed herein demonstrate that gemcitabine combinations are
highly active and well tolerated in the setting of metastatic disease, indicating an
important role for this agent in breast cancer. Optimizing use of such promising
agents and combinations throughout the many chapters of a patient's experience
with breast cancer is a central challenge in patient care. Recognition of the heterogeneity
in the biology and behavior of metastatic breast cancer will most certainly
imply heterogeneity in treatment strategies; this is indeed where the art and science
of medical oncology merge.