# Additive toxicity arising from combined use of immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with renal or endometrial carcinoma: Protocol for a rapid systematic review

## TL;DR

This study will review the safety of combining two cancer treatments in patients with kidney or endometrial cancer, focusing on severe side effects.

## Contribution

A novel rapid systematic review protocol to assess additive toxicity of ICI/TKI combinations in renal and endometrial carcinoma patients.

## Key findings

- The study will evaluate grade ≥3 treatment-related adverse effects of ICI/TKI combinations.
- Findings will be synthesized using meta-analysis and descriptive summaries.
- Results may guide treatment decisions for patients and providers.

## Abstract

The combined use of immune checkpoint inhibitors and tyrosine kinase inhibitors (ICI/TKI) is an effective treatment strategy for some cancers. A better understanding of the potential additive toxicity for ICI/TKI combinations is needed to inform patient and provider treatment decisions. We aim to evaluate the safety of ICI/TKI combinations for individuals with renal cell or endometrial carcinoma. This rapid systematic review (SR) protocol follows PRISMA guidelines. A systematic search will be designed, peer reviewed and executed by experienced information specialists (Cochrane Central, MEDLINE, Embase) to identify published SRs and primary studies published since the most recent SR search. Randomized, quasi- or non-randomized controlled trials and comparative cohort studies are eligible if they compare ICI/TKI combinations to monotherapy or standard of care in participants with renal cell or endometrial carcinoma. The primary outcome is grade ≥ 3 treatment-related adverse-effects. Studies will be screened, selected, extracted and assessed for risk of bias by a single reviewer and checked completely by a second. Where feasible and appropriate, we will pool studies separately by design and indication using meta-analysis and test robustness of effects using prespecified subgroup and sensitivity analyses. Results will be summarized descriptively and presented in tables and figures. (PROSPERO ID: CRD42023416388).•This will be a comprehensive systematic review of the additive toxicity arising from the combined use of ICI/TKIs in patients with renal-cell or endometrial carcinoma.•We will consider treatment-related, treatment-emergent adverse events (Grade 3 or higher).•Identified safety profile may be used to inform patient or provider treatment decisions.

This will be a comprehensive systematic review of the additive toxicity arising from the combined use of ICI/TKIs in patients with renal-cell or endometrial carcinoma.

We will consider treatment-related, treatment-emergent adverse events (Grade 3 or higher).

Identified safety profile may be used to inform patient or provider treatment decisions.

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