Fellow Cleveland Clinic Taussig Cancer Institute, United States
Background: Most patients with treatment-naïve metastatic renal cell carcinoma (mRCC) receive combination-based therapy with either two immune-oncology checkpoint inhibitors (IO/IO) or an IO agent in combination with a vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitor (IO/TKI). The rates of thromboembolism (TE) in these cohorts are not clearly described and can potentially impact decision-making between IO/IO and IO/TKI.
Methods: We conducted an IRB-approved cohort study of patients with mRCC treated with IO-based combinations between January 2015 and April 2021 at the Cleveland Clinic. TE events, including venous and arterial, were identified in each group. Competing risk regression was done to identify factors associated with the development of TE following therapy. All-cause mortality treated as a competing event.
Results: Of 220 patients identified, 92 (42%) received IO/TKI and 128 (58%) received IO/IO. Median age was 65 years, 78% male, 80% clear cell histology. Baseline characteristics were similar between the two groups. At a median follow-up of 23.0 months, 10.9% of all patients had a TE. The one-year incidence of TE was 8.0% (95% CI: 3.5-14.9%) with IO/TKI and 8.6% (95% CI: 4.6-14.3%) with IO/IO with similar incidence between the two groups (HR 0.742, 95% CI 0.318-1.732). Presence of TE was associated with decreased overall survival (HR 2.357, 95% CI 1.362-4.079). There was no difference in incidence of TE based on patient age, gender, race, prior history of TE, International Metastatic Renal Cell Carcinoma (IMDC) risk group, or Khorana score.
Conclusions: Incidence of TE is relatively high but appears to be similar between IO/IO and IO/TKI regimens in treatment-naïve mRCC. TE is also associated with decreased overall survival. Further investigations comparing these TE rates vs those in patients receiving IO and TKI monotherapies is ongoing.
