First-line therapy for metastatic renal cell carcinoma with pancreatic metastases: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

Abstract

317 Background: Metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) is characterised by heightened angiogenesis, which is associated with improved outcomes with vascular endothelial growth factor (VEGF) inhibitors. We aimed to compare the efficacy of first-line (1L) ipilimumab/nivolumab (IOIO) vs. anti-PD(L)1/anti-VEGF (IOVE) vs. VEGF monotherapy (VE) in mRCC patients with and without PM. Methods: We performed a retrospective analysis of patients with and without PM, using the IMDC. Sites of metastases were captured at initiation of 1L. Patients with PM could also have metastases at other sites. We studied overall survival (OS) from start of 1L therapy using Cox regression, adjusted for IMDC risk groups. Kaplan Meier survival curves were generated. Results: 543/7,634 (7%) patients had PM. Patients with PM in the overall population had improved OS compared to those without, 56 vs 25.6 months respectively (HR 0.63, 95% CI 0.55-0.73, p<0.0001). When examining the effect of PM within 1L options, those treated with IOVE exhibited a longer OS if PM were present vs absent, median not reached vs 45 months respectively (HR 0.41, 95% CI 0.18-0.93 p=0.03). This association was also seen in patients with treated with 1L VE, in those with PM vs absent, median 53.1 vs 25.1 months respectively (HR 0.65, 95% CI 0.55-0.76, p <0.0001). Contrastingly there was no difference in median OS of patients with or without PM in patients receiving IOIO, 41.4 vs 44.4 months respectively (HR 0.86, 95% CI 0.48-1.56, p=0.62). Comparing the outcomes between 1L therapies in patients with PM the median OS of IOVE vs VE was not reached vs 53.1 months respectively (HR 0.37, 95% CI 0.16-0.83 p=0.02). Conversely, upfront VE and IOIO had a similar median OS of 53.1 vs 41.4 months respectively (HR 0.81, 95% CI 0.45-1.47 p=0.49). We were unable to find any difference in OS between those treated with IOVE vs IOIO, median not reached vs 41.4 months respectively (HR 0.52 95%, CI 0.19-1.45, p=0.21), but the low event rate limited this interpretation. Conclusions: We found that the presence of PM leads to an indolent biological behavior and was associated with improved outcomes when 1L therapy included a VE component. PM patients had comparable OS outcomes on 1L VE and 1L IOIO therapy, but improved OS when treated with 1L IOVE. Anti-angiogenic therapy may be necessary to optimize outcomes in PM and this warrants prospective evaluation. [Table: see text]