TY - JOUR
T1 - A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma
AU - Siegel, David S.
AU - Martin, Thomas
AU - Wang, Michael
AU - Vij, Ravi
AU - Jakubowiak, Andrzej J.
AU - Lonial, Sagar
AU - Trudel, Suzanne
AU - Kukreti, Vishal
AU - Bahlis, Nizar
AU - Alsina, Melissa
AU - Chanan-Khan, Asher
AU - Buadi, Francis
AU - Reu, Frederic J.
AU - Somlo, George
AU - Zonder, Jeffrey
AU - Song, Kevin
AU - Stewart, A. Keith
AU - Stadtmauer, Edward
AU - Kunkel, Lori
AU - Wear, Sandra
AU - Wong, Alvin F.
AU - Orlowski, Robert Z.
AU - Jagannath, Sundar
PY - 2012/10/4
Y1 - 2012/10/4
N2 - 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/m2 intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m2 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 23.7% with median duration of response of 7.8 months. Median overall survival was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirtythree patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) 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 www.clinicaltrials.gov as #NCT00511238.
AB - 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/m2 intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m2 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 23.7% with median duration of response of 7.8 months. Median overall survival was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirtythree patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) 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 www.clinicaltrials.gov as #NCT00511238.
UR - http://www.scopus.com/inward/record.url?scp=84867295563&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-05-425934
DO - 10.1182/blood-2012-05-425934
M3 - Article
C2 - 22833546
AN - SCOPUS:84867295563
SN - 0006-4971
VL - 120
SP - 2817
EP - 2825
JO - Blood
JF - Blood
IS - 14
ER -