Comparison of outcomes between patients of African and European descent with metastatic renal cell carcinoma receiving immune checkpoint inhibitors.
Authors: Kaur Jasmeet , Hasler Jill S. , Handorf Elizabeth A. , Zibelman Matthew R. , Geynisman Daniel M. , Plimack Elizabeth R. , Ghatalia Pooja 
Published: January 2024

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Background: Immune checkpoint inhibitors (ICIs) and ICI/ tyrosine kinase inhibitor (TKI) combinations are standard front-line tx options for pts with metastatic renal cell carcinoma (mRCC). However, <1% of pts enrolled into trials studying these agents were of African descent. The primary outcome of this study was to compare real world progression-free survival (rwPFS) in Black and White pts, respectively, with mRCC receiving front-line ICI-based therapies versus sunitinib. Methods: Pts with mRCC who received front-line ICI-based tx or sunitinib after 2011 were included from the Flatiron Health electronic health record-derived database.Pt demographics and clinical characteristics, including age, gender, ECOG score, documented insurance, stage at diagnosis, IMDC score, and year of diagnosis were described and compared using t-tests for continuous data, and Chi-squared tests for categorical data. We compared rwPFS in pts who received ICI versus sunitinib in strata defined by race. We first performed separate analyses in Black and White patients, and then formally tested the interaction between treatment type and race using the full cohort. Unadjusted rwPFS was summarized using Kaplan-Meier curves with log-rank tests. Multivariable Cox proportional hazards models adjusted for relevant factors were used to assess associations with outcomes. Since the benefit of ICI-based treatments increases after 10 months, these models were stratified at 10 months for estimating treatment effects at each interval. Results: Of 2,592 eligible pts, 2,379 (91.8%) were White, and 213 (8.2%) were Black. Of these, 1453 (56%) received ICI-based tx and 1139 (44%) received sunitinib, the proportion being the same in both groups. IMDC favorable, intermediate/poor and unknown risk was noted among 6%, 77.5% and 16.4% of White patients and 3.3%, 86.8% and 9.9% of Black patients (p=0.01). More Whites than Blacks had nephrectomies (65.2% vs 55.9%). Median age was 64 years. In adjusted analysis, the hazard ratio (HR) of rwPFS for Whites receiving ICI-based tx vs sunitinib was 0.872 (p=0.036) in the first 10 months and 0.664 (p<0.001) after 10 months. In Blacks, the HR of rwPFS was 0.641 (p=0.067) in the first 10 months and 0.514 (p=0.072) after 10 months in pts receiving ICI-based tx vs sunitinib. There was no differential tx effect by race in the first 10 months or after 10 months (p=0.113, p=0.751, respectively). Similarly, upon subgroup analysis by tx, no differential tx effect was noted between Black and White pts receiving ICI/ICI or ICI/TKI based tx compared to sunitinib. Conclusions: No significant differential treatment effect was seen between White and Black pts receiving ICI-based tx. Smaller numbers of Black pts and reliance on self-reported race may have affected our results. These results indicate that ICI-based first line tx should be considered for both Black and White pts.