First-line PD-1 blockades combined with TKIs for metastatic non-clear cell renal cell carcinoma: a real-world multicenter retrospective study.

[BACKGROUND] Metastatic non-clear cell renal cell carcinoma (mnccRCC) are several rare subtypes of renal cell carcinoma, with standard treatment under investigation. This study retrospectively analyzes the largest Chinese cohort to assess the efficacy and safety of PD-1 blockades combined with tyrosine kinase inhibitors (TKIs) in mnccRCC.

[PATIENTS AND METHODS] A retrospective review was conducted on treatment-naive patients with mnccRCC who received first-line PD-1 blockades combined with TKIs or TKIs monotherapy. The baseline characteristics of the patients and adverse events (AEs) were collected. Efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

[RESULTS] The study enrolled 183 patients (99 TKI monotherapy, 84 combination therapy), with a median follow-up time of 20.0 (IQR, 11.1-32.4) months. ORR (32.1% vs. 20.2%) and DCR (82.1% vs. 55.6%) were improved in combination group compared with TKI group. Patients receiving combination therapy had a longer PFS and OS compared with those receiving TKI monotherapy [median PFS (95% CI): 19.1 (11.1-27.5) vs 8.1 (6.2-10.2)m, P < 0.001; median OS: not reached vs 44.1 (95% CI 27.4-70.0)m P = 0.017]. Subgroup analyses identified good performance status, non-chromophobe/Mit family translocation histologies and intermediate/poor IMDC classification derived pronounced survival advantages. The incidence of treatment-related AEs of grade three or higher was similar between the two groups (35.7% vs. 27.3%).

[CONCLUSIONS] PD-1 blockades combined with TKIs appeared an effective and safe choice in first-line treatment of mnccRCC, especially in individuals with good performance status, non-chromophobe/Mit family translocation histologies, and intermediate/poor IMDC classification.