# Real-world Evidence from a Retrospective Multicentre Analysis on First-line Therapy for Metastatic Papillary Renal Cell Carcinoma. A GUARDIANS Project

## TL;DR

This study analyzed real-world data on first-line treatments for metastatic papillary renal cell carcinoma and found that combining immune checkpoint inhibitors with tyrosine kinase inhibitors may be more effective than monotherapy.

## Contribution

The study provides real-world evidence supporting the use of immune checkpoint inhibitor plus tyrosine kinase inhibitor as a first-line treatment for metastatic papillary renal cell carcinoma.

## Key findings

- ICI-TKI combinations showed a median progression-free survival of 16.9 months, outperforming TKI monotherapy.
- 70% of patients experienced all-grade adverse events, with 33% discontinuing treatment due to side effects.
- The study highlights the need for prospective trials to optimize treatment strategies for metastatic pRCC.

## Abstract

Our real-word data support the use of a combination of immune checkpoint inhibitors and tyrosine kinase inhibitors in the first-line treatment of papillary renal cell carcinoma. However, prospective trials are needed to establish multimodal therapy in the future and further improve clinical outcomes for our patients.

Papillary renal cell carcinoma (pRCC) is a rare disease. The optimal treatment of metastatic pRCC is still unclear. We evaluated real-world treatment outcomes of first-line treatment in this cohort in Germany.

Patients with advanced or metastatic pRCC were eligible. Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events version 5.0. The overall response rate was accessed according to the local standard. Progression-free survival (PFS) was calculated from the start of treatment to progression or death. Descriptive statistics and Kaplan-Meier plots were utilised, where appropriate.

In total, 121 suitable patients (77% male) with a median age of 63 yr (quartiles 55, 70) were included. Prior nephrectomy was performed in 78%. Eastern Cooperative Oncology Group performance status 0–1 was reported in 74%. Lymphatic (68%) and pulmonary (42%) metastases were most common. Of the patients, 59% received first-line immune checkpoint inhibitor (ICI) combination therapies (ICI-ICI: 20%, tyrosine kinase inhibitor [TKI]-ICI: 39%), and 41% of patients received TKI monotherapy, predominantly sunitinib. The median follow-up time was 33.3 mo (interquartile range 14.8–46.7). The median PFS was 5.4 mo (95% confidence interval [CI]: 3.2–7.6) for ICI-ICI combinations, 16.9 mo (95% CI: 7.2–26.6) for ICI-TKI combinations, and 8.8 mo (95% CI: 7.0–10.7) for TKI monotherapy. Of all the patients, 70% and 35% experienced all-grade and grade 3–5 AEs, respectively. AEs of any cause led to discontinuation in 33% of patients.

TKI-based therapies are applied frequently in pRCC patients. Our data support the use of ICI plus TKI as a first-line standard for patients with pRCC. The major limitations were the retrospective data capture and short follow-up of our study. Additional analyses to tailor treatment strategies in patients with metastatic pRCC are warranted.

In this report, we looked at the outcome of first-line treatment of patients with metastatic papillary renal cell cancer (pRCC). Tyrosine kinase inhibitor (TKI)-based therapies are applied frequently in pRCC. Our data support the use of immune checkpoint inhibitor plus TKI as a first-line standard for patients with pRCC. However, further studies are needed to optimise treatment in patients with metastatic pRCC.