Clinical characteristics and determinants of primary refractory metastatic renal cell carcinoma (mRCC): An International Metastatic Database Consortium (IMDC) study.

Abstract

4549 Background: Immune checkpoint inhibitor (ICI)-based regimens, including ICI + ICI and ICI+VEGF-targeted therapy (VEGF-TT), represent the current standard of care for first line (1L) in mRCC. A subset of patients (pts) experiences primary refractory disease, defined as progressive disease (PD) as best response. The aim of this study is to investigate the clinical characteristics and determinants of pts with primary refractory mRCC. Methods: Pts with mRCC treated with 1L ICI-based regimens from the IMDC were included. Pts were categorized as primary refractory (PD as best response evaluated per RECIST 1.1 criteria) and non-primary refractory (stable disease or partial/complete response as best response). Baseline characteristics were compared using a Chi-Square test. Independent factors associated with primary refractory mRCC were identified using a logistic regression. Results: In total, 2001 pts were included, of which 1301 (65%) were treated with dual ICI, and 701 (35%) with ICI+VEGF-TT. Of 2001 pts, 494 (24%) experienced PD at first restaging. Primary refractory and non-primary refractory groups did not differ by age or gender. The primary refractory group had more pts treated with dual ICI (76 vs. 62%), more pts with poor IMDC risk (29 vs. 19%), and more pts with non-clear cell RCC (27 vs. 19%; all p < 0.001). The primary refractory group had shorter diagnosis to treatment interval (mean: 1.6 vs. 2.3 years), lower KPS (median: 80 vs. 90), higher rate of anemia (65% vs. 52%), neutrophilia (11% vs. 9%), and thrombocytosis (30 vs 22%; all p < 0.001). The primary refractory group had more liver (24 vs. 17%; p < 0.001), bone (39 vs 32%; p < 0.001) and lymph nodes metastasis (52 vs. 47%; p = 0.03) at the start of 1L therapy. On multivariable analysis, independent factors associated with primary refractory RCC were low KPS, and the presence of liver metastasis or bone metastasis (Table). Dual ICI regimen was associated with a 1.8-fold increase of primary refractory RCC. Conclusions: In pts with mRCC, low KPS and the presence of liver or bone metastasis are independent risk factors for the development of primary refractory disease. Primary refractory disease is more commonly observed in pts receiving dual ICI compared to those on ICI+VEGF-TT regimen. Multivariable analysis for independent factors associated with primary refractory RCC. OR Lower 95% CI Upper 95% CI p-value Diagnosis to treatment interval < 1 year (yes vs. no) 1.2 0.9 1.6 0.2 Anemia (yes vs. no) 1.37 1.1 1.8 0.03 Low KPS(<80: yes vs. no) 1.9 1.4 2.5 <0.001 Neutrophilia (yes vs. no) 1.3 1 1.8 0.09 Thrombocytosis (yes vs. no) 0.9 0.7 1.3 0.6 Liver metastasis (yes vs. no) 1.7 1.3 2.3 <0.001 Lymph Nodes metastasis (yes vs. no) 1.3 1 1.6 0.07 Bone metastasis (yes vs. no) 1.3 1.03 1.7 0.03 Dual ICI (vs. ICI+VEGF-TT) 1.8 1.37 2.4 <0.001 Non-clear cell RCC (vs. clear cell) 1.3 1 1.8 0.06 Nephrectomy (yes vs. no) 0.9 0.7 1.2 0.6