Characterization of Patients With Metastatic Renal Cell Carcinoma Experiencing Complete Response to First-line Therapies: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

Abstract

Purpose:Clinical trials have demonstrated higher complete response rates in the immuno-oncology–based combination arms than in the tyrosine kinase inhibitor arms in patients with metastatic renal cell carcinoma. We aimed to characterize real-world patients who experienced complete response to the contemporary first-line therapies.Materials and Methods:Using the International Metastatic Renal Cell Carcinoma Database Consortium, response-evaluable patients who received frontline immuno-oncology–based combination therapy or tyrosine kinase inhibitor monotherapy were analyzed. Baseline characteristics of patients and post-landmark overall survival were compared based on best overall response, as per RECIST 1.1.Results:A total of 52 (4.6%) of 1,126 and 223 (3.0%) of 7,557 patients experienced complete response to immuno-oncology–based and tyrosine kinase inhibitor therapies, respectively (P = .005). An adjusted odds ratio for complete response achieved by immuno-oncology–based combination therapy (vs tyrosine kinase inhibitor monotherapy) was 1.56 (95% CI 1.11-2.17; P = .009). Among patients who experienced complete response, the immuno-oncology–based cohort had a higher proportion of non–clear cell histology (15.9% and 4.7%; P = .016), sarcomatoid dedifferentiation (29.8% and 13.5%; P = .014), and multiple sites of metastases (80.4% and 50.0%; P < .001) than the tyrosine kinase inhibitor cohort. Complete response was independently associated with post-landmark overall survival benefit in both the immuno-oncology–based and tyrosine kinase inhibitor cohorts, giving respective adjusted hazard ratios of 0.17 (95% CI 0.04-0.72; P = .016) and 0.28 (95% CI 0.21-0.38; P < .001).Conclusions:The complete response rate was not as high in the real-world population as in the clinical trial population. Among those who experienced complete response, several adverse clinicopathological features were more frequently observed in the immuno-oncology–based cohort than in the tyrosine kinase inhibitor cohort. Complete response was an indicator of favorable overall survival.

Editorial Comment

“…Takemura et al leverage a robust, well-annotated, retrospective database to explore the real-world experience of patients exhibiting complete response (CR) to frontline therapy in mRCC, including those who received combination ICI agents. 2 Compared to the landmark trials leading to Food and Drug Administration approval of these ICI combinations, the authors report remarkably lower CR rates using these drugs. The heterogeneity in the International Metastatic Renal Cell Carcinoma Database Consortium database—such as variability in the type and duration of treatment received and baseline clinicopathological characteristics—is an important surrogate for the real-world experience and may help guide oncologists in counseling patients with mRCC.…”