Phase II trial and correlative genomic analysis of everolimus plus bevacizumab in advanced non-clear cell renal cell carcinoma Journal Article

Authors: Voss, M. H.; Molina, A. M.; Chen, Y. B.; Woo, K. M.; Chaim, J. L.; Coskey, D. T.; Redzematovic, A.; Wang, P.; Lee, W.; Selcuklu, S. D.; Lee, C. H.; Berger, M. F.; Tickoo, S. K.; Reuter, V. E.; Patil, S.; Hsieh, J. J.; Motzer, R. J.; Feldman, D. R.
Article Title: Phase II trial and correlative genomic analysis of everolimus plus bevacizumab in advanced non-clear cell renal cell carcinoma
Abstract: 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. © 2016 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 34
Issue: 32
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2016-11-10
Start Page: 3846
End Page: 3853
Language: English
DOI: 10.1200/jco.2016.67.9084
PROVIDER: scopus
PUBMED: 27601542
Notes: Article -- Export Date: 6 December 2016 -- Source: Scopus
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MSK Authors
  1. Sujata Patil
    383 Patil
  2. Joshua Chaim
    17 Chaim
  3. Robert Motzer
    744 Motzer
  4. Satish K Tickoo
    369 Tickoo
  5. Darren Richard Feldman
    171 Feldman
  6. Martin Henner Voss
    126 Voss
  7. Yingbei Chen
    221 Chen
  8. James J Hsieh
    114 Hsieh
  9. Michael Forman Berger
    380 Berger
  10. Victor Reuter
    900 Reuter
  11. William Lee
    38 Lee
  12. Kaitlin Marie Woo
    97 Woo
  13. Chung-Han   Lee
    37 Lee
  14. Patricia Ibai Wang
    12 Wang
  15. Devyn Taylor Coskey
    9 Coskey