Impact of Impaired Renal Function on the Efficacy and Safety of Second-Line Tyrosine Kinase Inhibitor Therapy After First-Line Immuno-Oncology Combination Therapy in Metastatic Renal Cell Carcinoma: A Japanese Multicenter Retrospective Study.

OBJECTIVES: To evaluate the effects of renal impairment at the time of second-line tyrosine kinase inhibitor (TKI) therapy initiation and rapid renal function decline during first-line immuno-oncology (IO) combination therapy on metastatic renal cell carcinoma (mRCC) patients treated with second-line TKIs.

METHODS: This multicenter retrospective study included 243 mRCC patients treated with first-line IO combination therapy, followed by second-line TKI therapy. Patients were divided into three groups using the estimated glomerular filtration rate (eGFR; mL/min/1.73 m2) at the time of second-line TKI therapy initiation: eGFR ≥ 60, 30 ≤ eGFR < 60, and eGFR < 30. The eGFR slope during first-line IO combination therapy was calculated using eGFR measurements when initiating first-line and second-line therapies. Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of renal impairment and eGFR slope on progression-free survival (PFS) and overall survival (OS).

RESULTS: The incidence rates of any grade and grade ≥ 3 adverse events were not significantly different among the three groups. Univariable analyses indicated that eGFR slope was not significantly associated with PFS or OS. Multivariable analyses suggested that moderate (30 ≤ eGFR < 60 mL/min/1.73 m2) and severe (eGFR < 30 mL/min/1.73 m2) renal impairment had no effects on shorter PFS, whereas severe renal impairment was independently and significantly associated with shorter OS.

CONCLUSIONS: TKIs can be safely used as a second-line treatment after first-line IO combination therapy in mRCC patients with renal impairment without sacrificing oncological outcomes, except for in patients with severe renal impairment.