# Adverse events of hepatic function disorder in Japanese patients with radically unresectable or metastatic renal cell carcinoma treated with pembrolizumab plus axitinib: a post-marketing surveillance study

## TL;DR

This study examines liver-related side effects in Japanese patients with advanced kidney cancer treated with pembrolizumab plus axitinib, finding consistent results with prior trials.

## Contribution

The study provides real-world evidence on hepatic adverse events of pembrolizumab plus axitinib in Japanese patients with metastatic RCC.

## Key findings

- 30.1% of patients experienced any grade hepatic function disorder adverse events.
- 15.0% of patients experienced grade ≥3 hepatic function disorder adverse events.
- No new safety signals were identified, consistent with prior clinical trial data.

## Abstract

Post-marketing surveillance focusing on hepatic function disorder was requested owing to its higher incidence in the pembrolizumab plus axitinib group than in the sunitinib group in KEYNOTE-426. We aimed to evaluate the prevalence and risk factors of adverse events (AEs) of hepatic function disorder in patients with unresectable/metastatic renal cell carcinoma (RCC) treated with pembrolizumab plus axitinib in real-world clinical practice in Japan.

Patients were observed for 9 months after starting treatment with pembrolizumab plus axitinib.

In total, 193 patients were included in the safety analysis set (median age, 70 years). Most patients did not have a history of hepatic function disorder before starting treatment (96.4%, 186/193). The median treatment period was 27.1 weeks. At the 9-month data cut-off, 62.2% (120/193) of patients discontinued treatment, the most common reason being any AE in 31.1% (60/193). The incidence of AEs of hepatic function disorder was 30.1% (58/193) for any grade and 15.0% (29/193) for grade ≥ 3. Most AEs of hepatic function disorder occurred within 3 months from starting treatment. AEs of hepatic function disorder were the reason for discontinuation of pembrolizumab in 9.3% (18/193) of patients; axitinib, 7.3% (14/193); and both pembrolizumab and axitinib, 5.2% (10/193). No background factors were identified as being associated with the occurrence of AEs of hepatic function disorder.

There were no new safety signals for AEs of hepatic function disorder, and the incidence was consistent with that reported in KEYNOTE-426, in Japanese patients with radically unresectable/metastatic RCC treated with pembrolizumab plus axitinib.

The online version contains supplementary material available at 10.1007/s10147-025-02708-2.