Clinical outcomes of patients with metastatic renal cell carcinoma with or without sarcomatoid differentiation treated with systemic therapy in a real-world Canadian setting
Alice Dragomir1, Ghady Bou-Nehme Sawaya1, Lori Wood2, Anil Kapoor3, Christian Kollmannsberger4, Denis Soulières5, Naveen Basappa6, Daniel Heng5, Eric Winquist7, Rodney H. Breau8, Christina Canil9, Vincent Castonguay10, Ramy Saleh11, Simon Tanguay1.
1Faculty of Medicine, McGill University, Montreal, QC, Canada; 2Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada; 3Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada; 4BC Cancer Agency Vancouver Cancer Centre, BC Cancer Agency, Vancouver, BC, Canada; 5Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, QC, Canada; 6Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; 7Department of Oncology, Western University, London, ON, Canada; 8Department of Surgery, University of Ottawa and Ottawa Hospital Research Institute Epidemiology Program, Ottawa, ON, Canada; 9The Ottawa Hospital, Ottawa, ON, Canada; 10Centre Hospitalier Universitaire de Québec, Quebec City, QC, Canada; 11Department of Internal Medicine, McGill University, Montreal, QC, Canada
Introduction: The objective of this study was to evaluate the impact of first-line systemic therapy on survival of metastatic renal cell carcinoma (mRCC) patients (pts) with or without sarcomatoid differentiation (SD) using real-world data.
Methods: The Canadian Kidney Cancer information system database was used to identify mRCC pts diagnosed from January 2011 to September 2021. Only pts with synchronous primary and metastatic disease, treated within 12 months from initial diagnosis, International Metastatic RCC Database Consortium (IMDC) intermediate-/high-risk, and a confirmed histology of RCC with documentation of presence/absence of SD were included. Pts were classified in two groups according to the presence or absence of SD defined at the time of nephrectomy. Within each of these groups, pts were compared by initial treatment received for mRCC: 1) vascular endothelial growth factor receptor (VEGFR) targeted treatment alone (TT) (sunitinib or pazopanib), or 2) immunotherapy-based treatment (IO). Inverse probability of treatment weighting using propensity scores was used to balance the groups for sex, age, Charlson comorbidity score, clear-cell histology, cytoreductive nephrectomy (before or after TT/IO), IMDC risk, sites, and number of organs with metastasis. Cox proportional hazards models were used to assess the impact of initial TT vs. IO on overall survival (OS) in pts with or without SD.
Results: A total of 470 pts were included in the study cohort: 352 pts were treated with TT and 118 pts were treated with IO. Median age was 62 years, 72% were male, and the majority had cytoreductive nephrectomy before ST (79%). In weighted analysis of the SD pts (40 IO and 94 TT patients), treatment with IO was associated with an increase in OS compared to TT (48 vs.18 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.29–0.92). In the non-SD pts (78 IO and 258 TT patients), the difference in survival was not proven between groups (60 vs. 36 months, HR 0.76, 95% CI 0.51–1.12).
Conclusions: Our study supports the hypothesis that, compared with targeted therapy alone, the magnitude of survival benefit with immunotherapy-based first-line systemic therapies is greater in pts with mRCC with SD.
