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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