Systemic therapy for advanced clear cell renal cell carcinoma after discontinuation of immune-oncology and VEGF targeted therapy combinations Journal Article


Authors: Ged, Y.; Gupta, R.; Duzgol, C.; Knezevic, A.; Shapnik, N.; Kotecha, R.; Voss, M. H.; Feldman, D. R.; Akin, O.; Patil, S.; Motzer, R. J.; Rini, B. I.; Lee, C. H.
Article Title: Systemic therapy for advanced clear cell renal cell carcinoma after discontinuation of immune-oncology and VEGF targeted therapy combinations
Abstract: Background: Several phase 3 studies reported positive results for combinations of Immune-Oncology (IO) and Vascular Endothelial Growth Factor (VEGF) targeted therapies in patients with metastatic clear cell Renal Cell Carcinoma (ccRCC). However, there are limited data on outcomes to systemic therapy after IO-VEGF combinations. Methods: A retrospective analysis was performed on patients with metastatic ccRCC treated at the Memorial Sloan Kettering Cancer Center and Cleveland Clinic who initiated systemic therapy post IO-VEGF including combinations with VEGF receptor (VEGFR) tyrosine kinase inhibitors (IO-TKI) and combinations with the anti-VEGF monoclonal antibody bevacizumab (IO-Bev). The study objectives were to evaluate the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) on systemic therapy post IO-VEGF. RECIST v1.1 criteria were used to determine radiological responses and progression. Survival estimates were evaluated with the Kaplan-Meier methods and the log-rank test from the start of systemic therapy post IO-VEGF to the event of interest. Results: A total of fifty-nine patients were treated post discontinuation of IO-VEGF regimens which included IO-Bev (n = 35; 59%) and IO-TKI (n = 24; 41%). Fifty-eight patients (98%) received IO-VEGF regimens as part of a clinical trial. Subsequent therapies included cabozantinib (n = 22; 37%), axitinib (n = 18; 31%), pazopanib (n = 4; 7%), lenvatinib and everolimus (n = 4; 7%), mTOR inhibitor monotherapy (n = 3; 5%), axitinib and dalantercept (n = 2; 3%), sunitinib (n = 1; 2%), sorafenib (n = 1; 2%), and treatment with agents on unreported clinical trials (n = 4; 7%). Patients treated on unreported clinical trials were excluded from the efficacy analysis. Post IO-VEGF, the ORR was 25% and median PFS was 12.0 months (95% CI, 8.2-24.5). Median OS was 24.5 months (95% CI, 12-NE) and 12 months OS rate was 63.3% (95% CI, 48.6-74.9). We observed no differences post IO-VEGF OS when comparing IO- TKI vs IO-Bev (Log-rank p = 0.73). Conclusions: Post IO-VEGF, most patients received VEGFR-TKIs. In this setting, VEGFR-TKIs demonstrated clinical activity and remain a viable option for salvage therapy after progression on IO-VEGF. © 2020 The Author(s).
Keywords: survival; vegf; rcc; immune-oncology; io combinations
Journal Title: BMC Urology
Volume: 20
ISSN: 1471-2490
Publisher: Biomed Central Ltd  
Date Published: 2020-07-02
Start Page: 84
Language: English
DOI: 10.1186/s12894-020-00647-w
PUBMED: 32616076
PROVIDER: scopus
PMCID: PMC7331268
DOI/URL:
Notes: Article -- Export Date: 3 August 2020 -- Source: Scopus
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MSK Authors
  1. Sujata Patil
    511 Patil
  2. Robert Motzer
    1248 Motzer
  3. Darren Richard Feldman
    345 Feldman
  4. Martin Henner Voss
    294 Voss
  5. Oguz Akin
    272 Akin
  6. Chung-Han   Lee
    157 Lee
  7. Andrea Knezevic
    107 Knezevic
  8. Yasser Mohamed Ali Ged
    19 Ged
  9. Natalie Shapnik
    16 Shapnik
  10. Cihan Duzgol
    19 Duzgol
  11. Ritesh Rajesh Kotecha
    94 Kotecha