TY - JOUR
T1 - Phase II trial and correlative genomic analysis of everolimus plus bevacizumab in advanced non-clear cell renal cell carcinoma
AU - Voss, Martin H.
AU - Molina, Ana M.
AU - Chen, Ying Bei
AU - Woo, Kaitlin M.
AU - Chaim, Joshua L.
AU - Coskey, Devyn T.
AU - Redzematovic, Almedina
AU - Wang, Patricia
AU - Lee, William
AU - Selcuklu, S. Duygu
AU - Lee, Chung Han
AU - Berger, Michael F.
AU - Tickoo, Satish K.
AU - Reuter, Victor E.
AU - Patil, Sujata
AU - Hsieh, James J.
AU - Motzer, Robert J.
AU - Feldman, Darren R.
N1 - Publisher Copyright:
© 2016 by American Society of Clinical Oncology.
PY - 2016/11/10
Y1 - 2016/11/10
N2 - Purpose The decreased effectiveness of single-agent targeted therapies in advanced non-clear cell renal cell carcinoma (ncRCC) compared with clear cell renal cell carcinoma (RCC) supports the study of combination regimens. We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC. Patients and Methods In this single-center phase II trial, treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks. The primary end point was progression-free survival (PFS) at 6 months. Correlative analyses explored candidate tissue biomarkers through next-generation sequencing. Results Thirty-five patients were enrolled with the following histologic subtypes: chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) RCC and unclassified RCC (uRCC, n = 23). The majority of patients had papillary growth as a major component (n = 14). For 34 evaluable patients, median PFS, overall survival, and objective response rate (ORR) were 11.0 months, 18.5 months, and 29%, respectively. PFS varied by histology (P < .001), and ORR was higher in patients with significant papillary (seven of 18) or chromophobe (two of five) elements than for others (one of 11). Presence of papillary features were associated with benefit, including uRCC, where it correlated with ORR (43% v 11%), median PFS (12.9 v 1.9 months), and overall survival (28.2 v 9.3 months; P < .001). Several genetic alterations seemed to segregate by histology. In particular, somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants. All five patients achieved treatment benefit. Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features. Distinct mutational profiles among ncRCCs vary according to specific histology.
AB - Purpose The decreased effectiveness of single-agent targeted therapies in advanced non-clear cell renal cell carcinoma (ncRCC) compared with clear cell renal cell carcinoma (RCC) supports the study of combination regimens. We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC. Patients and Methods In this single-center phase II trial, treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks. The primary end point was progression-free survival (PFS) at 6 months. Correlative analyses explored candidate tissue biomarkers through next-generation sequencing. Results Thirty-five patients were enrolled with the following histologic subtypes: chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) RCC and unclassified RCC (uRCC, n = 23). The majority of patients had papillary growth as a major component (n = 14). For 34 evaluable patients, median PFS, overall survival, and objective response rate (ORR) were 11.0 months, 18.5 months, and 29%, respectively. PFS varied by histology (P < .001), and ORR was higher in patients with significant papillary (seven of 18) or chromophobe (two of five) elements than for others (one of 11). Presence of papillary features were associated with benefit, including uRCC, where it correlated with ORR (43% v 11%), median PFS (12.9 v 1.9 months), and overall survival (28.2 v 9.3 months; P < .001). Several genetic alterations seemed to segregate by histology. In particular, somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants. All five patients achieved treatment benefit. Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features. Distinct mutational profiles among ncRCCs vary according to specific histology.
UR - http://www.scopus.com/inward/record.url?scp=84995513559&partnerID=8YFLogxK
U2 - 10.1200/JCO.2016.67.9084
DO - 10.1200/JCO.2016.67.9084
M3 - Article
C2 - 27601542
AN - SCOPUS:84995513559
SN - 0732-183X
VL - 34
SP - 3846
EP - 3853
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 32
ER -