Progression-free survival after second line of therapy for metastatic clear cell renal cell carcinoma in patients treated with first-line immunotherapy combinations Research Letter


Authors: Fitzgerald, K. N.; Duzgol, C.; Knezevic, A.; Shapnik, N.; Kotecha, R.; Aggen, D. H.; Carlo, M. I.; Shah, N. J.; Voss, M. H.; Feldman, D. R.; Motzer, R. J.; Lee, C. H.
Title: Progression-free survival after second line of therapy for metastatic clear cell renal cell carcinoma in patients treated with first-line immunotherapy combinations
Abstract: Immunotherapy (IO)-based combinations used to treat metastatic clear cell renal cell carcinoma (ccRCC) include dual immune checkpoint inhibition with ipilimumab and nivolumab (IO/IO) and several combinations of vascular endothelial growth factor receptor–targeting tyrosine kinase inhibitors (TKIs) with an immune checkpoint inhibitor (TKI/IO). IO/IO and TKI/IO approaches have not been compared directly, and it is unknown whether patients who do not respond to first-line IO/IO can salvage long-term survival by receiving a second-line TKI. Progression-free survival after second-line therapy (PFS-2) evaluates the ability to be salvaged by second-line therapy. We retrospectively evaluated 173 patients treated with first-line IO/IO or TKI/IO for metastatic ccRCC at Memorial Sloan Kettering Cancer Center and report PFS-2, overall survival, and response to second line of therapy (ORR2nd) for groups defined by first-line category. Although ORR2nd was significantly higher with IO/IO than with TKI/IO (47% vs 13%, p < 0.001), there was no significant difference in median PFS-2 for TKI/IO versus IO/IO (44 vs 23 mo, log-rank p = 0.1) or restricted mean survival time (RMST) for PFS-2 when adjusted for propensity score (33 vs 30 mo; difference 2.6 mo [95% confidence interval {CI}: –2.6, 7.9]; p = 0.3). There was also no significant difference in RMST for overall survival when adjusted for propensity score (38 vs 37 mo; group difference 1.0 mo [95% CI: –3.4, 5.5]; p = 0.7). These findings do not support a change in current utilization practices for IO/IO and TKI/IO treatment strategies for ccRCC. Patient summary: In cases of metastatic clear cell renal cell carcinoma, no significant difference was observed in progression-free survival after second line of therapy between patients receiving ipilimumab plus nivolumab and those receiving a combination of a tyrosine kinase inhibitor and an immune checkpoint inhibitor. © 2022 European Association of Urology
Keywords: controlled study; treatment response; vascular endothelial growth factor a; retrospective studies; major clinical study; overall survival; sunitinib; drug withdrawal; ipilimumab; progression free survival; protein kinase inhibitor; lung disease; pathology; retrospective study; renal cell carcinoma; kidney neoplasms; protein kinase inhibitors; cancer center; immunotherapy; kidney tumor; carcinoma, renal cell; cardiovascular disease; vasculotropin a; pazopanib; liver disease; axitinib; tyrosine kinase inhibitor; neurologic disease; disease exacerbation; colorectal disease; progression-free survival; adverse event; metastatic renal cell carcinoma; second-line treatment; first-line treatment; cabozantinib; nivolumab; lenvatinib; humans; human; article; pembrolizumab; mean survival time; immune checkpoint inhibitors; avelumab; progression-free survival after second line of therapy
Journal Title: European Urology
Volume: 83
Issue: 3
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2023-03-01
Start Page: 195
End Page: 199
Language: English
DOI: 10.1016/j.eururo.2022.10.017
PUBMED: 36344318
PROVIDER: scopus
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Chung-Han Lee -- Source: Scopus
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MSK Authors
  1. Robert Motzer
    1243 Motzer
  2. Darren Richard Feldman
    342 Feldman
  3. Martin Henner Voss
    288 Voss
  4. Maria Isabel Carlo
    162 Carlo
  5. Chung-Han   Lee
    157 Lee
  6. Andrea Knezevic
    106 Knezevic
  7. Natalie Shapnik
    16 Shapnik
  8. Cihan Duzgol
    19 Duzgol
  9. Ritesh Rajesh Kotecha
    92 Kotecha
  10. David Henry Aggen
    57 Aggen
  11. Neil Jayendra Shah
    85 Shah