# Correlation Between Treatment‐Related Adverse Events and Efficacy of Camrelizumab in Combination With Apatinib in Patients With Unresectable Hepatocellular Carcinoma

## TL;DR

This study found that immune-related side effects did not predict treatment success, but high blood pressure from apatinib was linked to better outcomes in liver cancer patients.

## Contribution

The study reveals that apatinib-related hypertension, not immune-related adverse events, correlates with improved treatment efficacy in hepatocellular carcinoma.

## Key findings

- Patients with apatinib-related hypertension had significantly better objective response and disease control rates.
- Apatinib-related hypertension was associated with longer progression-free and overall survival.
- Immune-related adverse events did not predict improved survival outcomes despite higher response rates.

## Abstract

The relationship between treatment‐related adverse events (TRAEs) and efficacy in patients receiving immune checkpoint inhibitors (ICIs) combined with anti‐angiogenic therapy remains unclear. This study aims to investigate the potential correlation between TRAEs and efficacy in patients with unresectable hepatocellular carcinoma (uHCC) treated with the combination of camrelizumab and apatinib.

We conducted an analysis of efficacy and safety data obtained from 189 patients with uHCC enrolled in a phase II trial. All patients received intravenous camrelizumab 200 mg every 2 weeks and oral apatinib 250 mg once daily in 4‐week cycles. Efficacy was evaluated based on objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS). We described the profiles of TRAEs and analyzed the correlation between TRAEs and treatment efficacy. To mitigate the impact of immortal time bias, landmark analysis and time‐dependent Cox regression analysis were employed to assess the correlation between immune‐related adverse events (irAEs) and survival outcomes.

As of March 10, 2021, irAEs of any grade were reported in 88 (46.6%) patients, with 17 (9.0%) patients experiencing grade 3–4 irAEs. The median onset time for any grade irAEs was 17.4 weeks. Apatinib‐related adverse events (AEs) of any grade were reported in 188 (99.5%) patients. Among them, 139 (73.5%) patients experienced any grade of apatinib‐related hypertension, while 65 (34.4%) patients had grade 3–4 hypertension. Patients who experienced irAEs exhibited significantly higher ORR and DCR, but the onset of irAEs occurred later than the time of PR or CR in 75.0% (30/40) of patients. Furthermore, in the landmark analysis and time‐dependent Cox regression analysis, no significant differences in survival outcomes were observed between patients with irAEs and those without. Notably, patients with apatinib‐related hypertension demonstrated better ORR (38.1% vs. 18.0%, p = 0.009) and DCR (84.2% vs. 60.0%, p < 0.001), as well as longer PFS (6.5 vs. 3.7 months, p = 0.001) and OS (23.0 vs. 15.1 months, p = 0.03).

In this study, the occurrence of irAEs did not predict the efficacy of camrelizumab in combination with apatinib, likely due to the decreased incidence and delayed occurrence. On the other hand, apatinib‐related hypertension was associated with improved treatment efficacy.