Site-specific patterns of early response to nivolumab plus ipilimumab therapy in advanced renal cell carcinoma patients compared with tyrosine-kinase inhibitors

Int Immunopharmacol. 2022 Nov 17;113(Pt B):109443. doi: 10.1016/j.intimp.2022.109443. Online ahead of print.

Abstract

Objective: This study aimed to identify patterns of early response to nivolumab and ipilimumab combination therapy (Nivo+Ipi) in primary and metastatic sites of advanced renal cell carcinoma (RCC).

Method: RCC patients treated with Nivo+Ipi or tyrosine-kinase inhibitors (TKIs) as first-line therapy were included. To exclude selection bias due to patient characteristics, baseline clinical data was adjusted by inverse probability of treatment weighting (IPTW). Overall response rate (ORR) and lesional response rates (LRR) in primary and metastatic sites were determined by measuring tumor diameters on serial CT images according to Response Evaluation Criteria in Solid Tumors, version 1.1.

Results: 33 patients were treated with Nivo+Ipi and 39 with TKIs as first-line therapy. After IPTW-adjusted analysis, ORR during the first 24 weeks of treatment was significantly higher in Nivo+Ipi group than in TKIs group (45.5% versus 21.7%, p < 0.01). LRR of the primary tumor tended to be higher in Nivo+Ipi group than in TKI group (14.8% versus 4.4%, p = 0.06). Mean LRR of all metastatic sites was not significantly different between the two groups, but tumor shrinkage rate of lung metastasis was significantly higher in Nivo+Ipi group than in TKIs group (68.5% versus -12.7%, p < 0.01). Univariate and multivariate analyses identified lung metastasis as the independent factor associated with prolonged progression-free survival and with higher ORR.

Conclusion: Our study found that lung metastasis of advanced RCC exhibited early response to Nivo+Ipi therapy. Further studies are warranted to verify whether site-specific early response predicts overall survival benefit in advanced RCC patients treated with Nivo+Ipi.

Keywords: Nivolumab and ipilimumab combination; Renal cell carcinoma; Site-specific early response.