Clinical effectiveness of second-line TKI plus PD-1 following targeted therapy in patients with metastatic non-clear cell renal cell carcinoma: A real-world study.

Abstract

e16523 Background: Non-clear cell renal carcinoma (nccRCC) usually had a poorer response to tyrosine kinase inhibitors (TKIs) due to its heterogeneity and rarity. The combination of immunotherapy with TKIs has shown promising efficacy in ccRCC. However, for nccRCC failed standard first-line TKI therapy, the second-line option is still limited. This real-world study aimed to evaluate the efficacy of immune-targeted combination therapy versus TKI monotherapy as the second-line regimen in patients with metastatic nccRCC who failed first-line TKI therapy. Methods: Demographic and clinicopathological data of patients with metastatic nccRCC who were admitted into the Sun Yat-sen University Cancer Center between October, 2011 and September, 2020 were retrospectively collected. All patients failed in first-line TKI therapy and received second-line TKI alone (TKI group) or TKI plus PD-1 therapy (combination group). Efficacy including the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) was calculated. The differences on baseline characteristics and efficacy between the two groups were compared. Results: Totally 67 patients were included, with a median age of 50 (interquartile 37-60) years. The median follow-up time was 32.7 (interquartile 21.6-53.0) months. The overall ORR, DCR was 37.3% and 56.7%, respectively. The overall second-line PFS was 7.2 (95% CI: 5.8-8.5) months and OS was 53.2 (18.4-88.0) months. Baseline characteristics between the combination group (n = 45) and the TKI group (n = 22) did not differ significantly except that the combination group had more proportion of liver metastasis (20.9% vs 4.5%, P = 0.025). The combination group had a significantly longer PFS compared with the TKI group [median PFS (95% CI): 9.2 (6.4-12.0) vs 5.2 (2.9-7.5) months, P = 0.001]. Similarly, ORR (48.9% vs 13.6, P = 0.005) and DCR (71.1% vs 27.3%, P = 0.001) was remarkably improved in the combination group. The superior efficacy over TKI monotherapy was more prominent in the younger (< 60 years), male, and patients with lower KPS, IMDC intermediate/poor-risk, non-hereditary RCC and multiple metastatic sites. Conclusions: Immune-targeted combination therapy was effective in the treatment of metastatic nccRCC who failed first-line TKIs.[Table: see text]