Real-world practice patterns, treatment-related toxicity, and survival outcomes in older patients with metastatic renal cell carcinoma: Results from the Canadian Kidney Cancer information system (CKCis).
Authors: Curry Lauren Caitlin , Ghosh Sunita , Arenovich Erica , Tanguay Simon , Lalani Aly-Khan A. , Heng Daniel Yick Chin , Bhindi Bimal , Basappa Naveen S. , Graham Jeffrey , Bjarnason Georg A. , Breau Rodney H , Castonguay Vincent , Soulieres Denis , Pouliot Frederic , Bosse Dominick , Kollmannsberger Christian K. , Finelli Antonio , Fallah-rad Nazanin , Soleimani Maryam 
Published: January 2024

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Background: There is a paucity of data with respect to optimal management of metastatic renal cell carcinoma (mRCC) in older adults. Real world data may help close this knowledge gap and improve care for older patients with mRCC. Methods: The Canadian Kidney Cancer information system (CKCis) was utilized to identify patients with mRCC, categorizing them as either older (defined as age ≥75 years) or younger (age <75 years). We compared first line (1L) mRCC management strategies and treatment-related toxicities. Secondary outcomes were overall survival (OS) and time to treatment discontinuation (TTD). Chi-Square and Fisher’s Exact tests were used to compare groups, and survival outcomes were measured by Kaplan-Meier method. Cox’s proportional hazard ratio (HR) were reported by age adjusting for IMDC risk groups, histology, and Charlson Comorbidity Index (CCI) for OS and TTD. Results: 2576 patients were included (n=2203 <75 years old; n=373 ≥75 years old). Baseline demographics were comparable between groups, though older patients had more comorbidities (5+, 95% vs. 67%, p<0.0001) and more frequently had Karnofsky Performance Status <70% (18% vs. 13%, p=0.01). Older patients underwent metastasectomy less frequently (15% vs. 25%, p=0.0001) and were less likely to be enrolled in clinical trials (10% vs. 24%, p<0.0001). Older patients received 1L tyrosine kinase inhibitor (TKI) monotherapy more frequently (79% vs. 69%, p<0.0001) than immune checkpoint inhibitor (ICI)-based treatment, even when adjusted by year to account for changes in practice patterns in the post-ICI era (65% vs. 44%, p<0.0001). Amongst all patients, the TKI monotherapy most frequently prescribed was sunitinib, though older patients were more likely to receive pazopanib than younger patients ( p<0.0001). Amongst all patients who received 1L ICI-based treatment, there was no difference in the type of ICI regimen (i.e. doublet ICI versus ICI plus TKI) prescribed when compared by age ( p=0.61). Older patients did not experience more frequent treatment-related toxicities with ICI-based treatment. They did however experience more grade 3+ toxicity with TKI monotherapy. Older patients had shorter OS even when controlling for IMDC score, CCI and histology (HR 1.21, 95% CI 1.03-1.43, p=0.02). There was no difference in TTD by groups. Conclusions: Patients ≥75 years of age received TKI monotherapy more frequently than those <75 years of age, though when they received ICI-based regimens, they did not experience more treatment-related toxicities nor more dose modifications. Clinicians should individualize treatments for older patients not solely based on age, but after discussion of all available options in a patient-centered manner, considering comorbidities, disease burden, and patient preferences.