TY - JOUR
T1 - A phase II multi-center study of bevacizumab in combination with ixabepilone in subjects with advanced renal cell carcinoma
AU - Burotto, Mauricio
AU - Edgerly, Maureen
AU - Velarde, Margarita
AU - Balasubramaniam, Sanjeeve
AU - Drabkin, Harry
AU - Gormaz, Juan G.
AU - O’Sullivan, Ciara
AU - Madan, Ravi
AU - Fojo, Tito
N1 - Publisher Copyright:
© AlphaMed Press 2017.
PY - 2017/8
Y1 - 2017/8
N2 - Background. Treatment of metastatic renal cell carcinoma (mRCC) remains suboptimal. Preclinical data have previously shown that ixabepilone, a microtubule-stabilizing agent approved for the treatment of breast cancer, is active in taxanesensitive and -resistant cells. In this single-arm phase II trial, we investigated a combination of ixabepilone plus bevacizumab in patients with refractory mRCC. Methods.We enrolled 30 patients with histologically confirmed mRCC, clear cell subtype, who had not been previously treated with ixabepilone or bevacizumab but had received at least one prior U.S. Food and Drug Administration (FDA)-approved treatment for renal cell carcinoma (RCC). The treatment regimen consisted of 6 mg/m2 ixabepilone per day for 5 days and 15 mg/kg bevacizumab every 21 days. After 6 cycles, the treatment interval could be extended to every 28 days. The primary endpoint was the objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and the toxicity of the combination. Results. The median number of prior therapies was two (range per patient one to five). Patients received a median of 8 cycles of ixabepilone plus bevacizumab (range 2-54). The median follow-up was 36.4 months (range 23.5-96.5). Nineteen patients (63.3%) had stable disease as a best response. Three patients (10%) had a partial response. The median PFS was 8.3 months (95% confidence interval [CI], 4.9-10.6) and the median OS was 15.0 months (95% CI, 11.3-28.8). The total number of cycle for safety evaluation was 289. Grade 3/4 adverse events (>5% incidence) included lymphopenia (16.7%), hypertension (6.7%), and leukopenia (6.7%). Conclusion. The combination of ixabepilone and bevacizumab was well tolerated, with modest activity in second - or later-line mRCC, but it is not recommended as a therapy without further clinical development. Alternative combinations with these agents could be explored in future studies.
AB - Background. Treatment of metastatic renal cell carcinoma (mRCC) remains suboptimal. Preclinical data have previously shown that ixabepilone, a microtubule-stabilizing agent approved for the treatment of breast cancer, is active in taxanesensitive and -resistant cells. In this single-arm phase II trial, we investigated a combination of ixabepilone plus bevacizumab in patients with refractory mRCC. Methods.We enrolled 30 patients with histologically confirmed mRCC, clear cell subtype, who had not been previously treated with ixabepilone or bevacizumab but had received at least one prior U.S. Food and Drug Administration (FDA)-approved treatment for renal cell carcinoma (RCC). The treatment regimen consisted of 6 mg/m2 ixabepilone per day for 5 days and 15 mg/kg bevacizumab every 21 days. After 6 cycles, the treatment interval could be extended to every 28 days. The primary endpoint was the objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and the toxicity of the combination. Results. The median number of prior therapies was two (range per patient one to five). Patients received a median of 8 cycles of ixabepilone plus bevacizumab (range 2-54). The median follow-up was 36.4 months (range 23.5-96.5). Nineteen patients (63.3%) had stable disease as a best response. Three patients (10%) had a partial response. The median PFS was 8.3 months (95% confidence interval [CI], 4.9-10.6) and the median OS was 15.0 months (95% CI, 11.3-28.8). The total number of cycle for safety evaluation was 289. Grade 3/4 adverse events (>5% incidence) included lymphopenia (16.7%), hypertension (6.7%), and leukopenia (6.7%). Conclusion. The combination of ixabepilone and bevacizumab was well tolerated, with modest activity in second - or later-line mRCC, but it is not recommended as a therapy without further clinical development. Alternative combinations with these agents could be explored in future studies.
KW - Adult
KW - Aged
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Bevacizumab
KW - Bridged-Ring Compounds
KW - Carcinoma, Renal Cell
KW - Disease-Free Survival
KW - Epothilones
KW - Female
KW - Humans
KW - Middle Aged
KW - Neoplasm Staging
KW - Taxoids
UR - http://www.scopus.com/inward/record.url?scp=85027297035&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2017-0211
DO - 10.1634/theoncologist.2017-0211
M3 - Article
C2 - 28679644
AN - SCOPUS:85027297035
SN - 1083-7159
VL - 22
SP - 888-e84
JO - Oncologist
JF - Oncologist
IS - 8
ER -