Real-world assessment of clinical outcomes of first-line treatment in metastatic papillary Renal Cell Carcinoma

Abstract

Background: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC), representing up to 15% of RCC cases. Phase 2 trials have evaluated first-line (1 L) immunotherapy (IO)-based treatment in nccRCC, but with heterogeneous cohorts and limited comparative data. The specific value of IO for metastatic pRCC (mpRCC) remains unquantified.

Methods: We analyzed prospectively collected data from the Canadian Kidney Cancer Information System (CKCis) to assess the efficacy of 1 L systemic therapy in mpRCC with IO-based regimens versus tyrosine kinase inhibitors (TKI). The primary endpoint was time-to-treatment failure (TTF). Secondary endpoints included overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Analyses were adjusted (adj) for IMDC risk groups.

Results: From 2011 to 2024, 197 mpRCC patients received 1 L therapy: 70 with IO (alone or in combination) and 127 with TKI. Median follow-up was 21.6 months. Median TTF was 9.9 months with IO vs 5.9 months with TKI (adjHR: 0.62 [0.43-0.91] p = 0.01). Median OS was 36.9 months with IO vs 23.2 months with TKI (adjHR: 0.54 [0.3-0.9], p = 0.018). ORR was 37% with IO vs 23% with TKI (adjOR: 2.2 [0.95-5.2] p = 0.07). The TKI-IO subgroup showed the longest TTF (16.9 months, adjHR: 0.47 [0.26-0.85], p = 0.01) and OS (not reached, adjHR: 0.26 [0.08-0.83], p = 0.02), compared to TKI. Grade 3-5 TRAEs occurred in 31% (IO) vs. 27% (TKI).

Conclusion: This real-world study highlights the benefit of IO-based treatment in mpRCC, particularly in the TKI-IO subgroup. Our findings may inform further trials evaluating 1 L IO in mpRCC.

Keywords: CKCis; TKI; first-line systemic treatment; immunotherapy; metastatic papillary renal-cell cancer.