Therapeutic outcome of combination therapy using immune-checkpoint inhibitors and tyrosine kinase inhibitors for metastatic non-clear-cell renal cell carcinoma.

INTRODUCTION: We aimed to clarify the therapeutic outcome of combination therapy using immune-checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs) for metastatic non-clear-cell renal cell carcinoma (nccRCC).

METHODS: We have been retrospectively investigating the therapeutic efficacy and prognosis in 36 patients with metastatic nccRCC undergoing combination therapy using two ICIs, ipilimumab plus nivolumab (ICI-ICI), and ICI plus TKI (ICI-TKI), at Kobe University and affiliated institutions since 2018. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse event (AE) were compared.

RESULTS: The first-line regimens was ICI-ICI regimens in 26 cases and ICI-TKI regimens in 10 cases. The ORRs in the ICI-ICI and ICI-TKI groups were 34.6 and 30.0%, respectively (p=0.9433). The 50% PFS for the ICI-TKI group was 9.7 months, significantly longer than that for the ICI-ICI group (4.6 months, p=0.0499), and there was no significant difference in OS between them (p=0.3984). There was no significant difference in the occurrence rate of AE for below grade 2 (p=0.8535) nor above grade 3 (p=0.3786) between the ICI-ICI and ICITKI groups.

CONCLUSIONS: From our analysis of real-world data, a better outcome of PFS was expected in the ICI-TKI group compared with that in the ICI-ICI group, while there was no significant difference in OS or ORR.