OBJECTIVES: 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 was used to identify mRCC pts diagnosed from Jan 2011 to April 2022. Only pts with synchronous primary and metastatic disease, 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 initial treatment received for mRCC: (1) targeted treatment (TT) or (2) immunotherapy-based treatment (IO). Within each of these groups, pts were subclassified by presence or absence of SD based on their nephrectomy specimen. Inverse probability of treatment weighting using propensity scores was used to balance the groups for sex, age, Charlson comorbidity score, clear cell histology, 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) and by SD status.

RESULTS: A total of 650 pts were included in the study cohort: 484 pts were treated with TT and 166 pts were treated with IO. In weighted analysis of the SD pts (113 TT and 50 IO patients), treatment with IO was associated with an increase in OS compared to TT (median of 36 versus 18 months, HR 0.50, 95% CI 0.31-0.82). In the non-SD pts (371 TT and 116 IO patients), patients treated with IO had an improved survival compared to patients treated with TT (median of 72 versus 36 months, HR 0.64, 95% CI 0.45-0.92).

CONCLUSIONS: In conclusion, mRCC patients with or without SD have an improved survival when treated with IO-based first-line systemic therapies compared to TT-based first-line treatments.