# Pembrolizumab in Practice: Assessing Safety and Effectiveness Through a Retrospective Frame

## TL;DR

This study evaluates pembrolizumab's effectiveness and safety in treating various cancers over five years, finding it generally effective and well-tolerated with manageable side effects.

## Contribution

The study provides real-world evidence of pembrolizumab's effectiveness and safety across a diverse range of cancers and identifies lenvatinib as a factor increasing toxicity.

## Key findings

- Pembrolizumab showed an objective response rate of 14.5% and disease control rate of 61.3% across 22 cancer types.
- Breast cancer patients had the best outcomes with 33.3% achieving complete or partial response.
- Adverse events occurred in 80.2% of patients, mostly mild to moderate, and patients with adverse reactions had better clinical outcomes.

## Abstract

Introduction

Immune evasion is one of the surest methods to initiate an effective antitumour response. Programmed cell death protein 1 (PD-1) is a highly expressed immune checkpoint receptor on lymphocytes and plays an important role in regulating T-cell responses to reduce damage to surrounding normal tissues. This methodology has been successfully tried in metastatic non-small-cell lung cancer (NSCLC), renal cell cancer, urothelial cancer, bladder cancer, colon cancer, etc.

Study aim

The aim of this study was to determine the effectiveness of pembrolizumab in various cancers over the last five years and to analyse the pattern of Adverse Drug Reactions (ADR) in patients treated with pembrolizumab.

Methodology

This is a retrospective study with patients who received at least one dose of pembrolizumab from August 31st, 2019, to July 31st, 2024. Demographic data, details of pembrolizumab therapy, documented adverse reactions, and patient response as per RECIST (Response Evaluation Criteria in Solid Tumours) criteria were noted.

Results

A total of 111 patients treated with pembrolizumab across 22 cancer types received 1,238 treatment cycles (mean 11 cycles per patient). Pembrolizumab demonstrated meaningful clinical effectiveness, with an objective response rate (ORR) = 14.5% and a disease control rate (DCR) is 61.3% across a heterogeneous cancer cohort. Among individual malignancies, breast cancer patients showed the most favorable outcomes, with 33.3% achieving complete or partial response and 55.6% maintaining stable disease.

Adverse events, including 21 immune-mediated events, were observed in 80.2% of patients. The majority of adverse reactions were mild to moderate (Grade 1-2). Five patients developed Grade 3 thrombocytopenia, all of whom were successfully rechallenged. Concomitant lenvatinib therapy was significantly associated with increased toxicity (p=0.041), particularly thyroid dysfunction. Notably, patients who developed adverse reactions demonstrated better clinical outcomes than those without toxicity.

Conclusion

Pembrolizumab demonstrated meaningful effectiveness with an ORR of 14.5%, a disease control rate of 61.3%, and a generally favorable safety profile, with most adverse reactions being mild to moderate and immune-related toxicities manageable. Increased vigilance is required when combined with lenvatinib due to higher thyroid dysfunction risk. Overall, pembrolizumab remains an effective and well-tolerated option across diverse cancers, underscoring the importance of careful patient selection and close monitoring to optimize therapeutic outcomes.