Changes in outcome of patients with advanced non-clear cell renal cell carcinoma from the tyrosine kinase inhibitor era to the immuno-oncology era

Abstract

Background: The therapeutic benefit of immuno-oncology (IO) therapy for patients with advanced non-clear-cell renal cell carcinoma (nccRCC) remains unclear.

Patients and methods: We reviewed clinical data from 93 patients with advanced nccRCC who received first-line systemic therapy including IO combination therapy and tyrosine kinase inhibitor (TKI) monotherapy at our affiliated institutions. Patients were divided based on the period when the treatment was implemented as the standard of care into the IO and TKI eras. Survival and tumor response outcomes were compared between the IO and TKI eras.

Results: Of the 93 patients, 50 (54%) and 43 (46%) were categorized as IO era and TKI era groups, respectively. Progression-free survival (PFS) and overall survival (OS) were significantly longer in the IO era than in the TKI era (median PFS: 8.97 vs. 4.96 months, p = 0.0152; median OS: 38.4 vs. 13.5 months, p = 0.0001). After the adjustment using other covariates, the treatment era was an independent factor for PFS (hazard ratio: 0.59, p = 0.0235) and OS (hazard ratio: 0.27, p < 0.0001). Objective response and disease control rates was not significantly different between the treatment eras (26% vs. 16.3%, p = 0.268; 62% vs. 62.8%, p = 0.594).

Conclusion: The implementation of IO therapy was significantly associated with longer survival in the nccRCC population. Further studies are needed to establish a more effective treatment strategy in this population using multiple regimens of IO combination therapy.

Keywords: Avelumab; Axitinib; Cabozantinib; Immune checkpoint inhibitor; Ipilimumab; Lenvatinib; Nivolumab; Papillary renal cell carcinoma; Pembrolizumab.