Safety Profile of Combination Treatment with Radiotherapy and Immune Checkpoint Blockades: A Multi-Institute Real World Experience

Abstract

Immune checkpoint blockades have become widely used in recent years and have been approved as standard first-line and subsequent treatment for different types of malignancy. Combination treatment with irradiation also showed promising results in previous clinical studies. However, the treatment toxicities of this combination strategy have not been well defined. We hypothesized combination therapy does not add additional toxicities to immune checkpoint blockade alone. The study aims to investigate the safety profile of combination treatment with immune checkpoint blockade and radiotherapy in all type cancer patients. We conducted a population-based retrospective cohort study using the electronic medical records from three hospitals in Taiwan from January 01, 2015, to December 31, 2020. Baseline demographic data, laboratory examination, and treatment history were collected. Patients with radiotherapy exposure and immune checkpoint blockade were enrolled. The primary endpoint was all grade toxicities. All patients were monitored from the date of initiating immune checkpoint blockade or irradiation until the event of death, loss follow-up, or any defined adverse events. All data was managed using SAS v.9.4 software. Kaplan-Meier estimators and cox proportional hazard regression models were used to compute the safety profile of combination treatment. The statistical significance was considered with a p-value <0.05. A total of 305 cases, including 181 male patients and 124 female patients, received combination treatment with immune checkpoint blockade and radiotherapy with different time sequences. The most common cancer types are lung cancer (33.1%) followed by gastroesophageal cancer (16.7%) and hepatobiliary cancer (13.8%). The most common toxicities were arthralgia (25.9%), followed by enterocolitis (23.6%), and anemia (21%). 11 cases (3.6%) developed pneumonitis, 5 cases (1.6%) developed myocarditis, and 5 cases (1.6%) developed hepatitis during combination treatment. There is no evidence leads to additional toxicities based on current real-world experience. Severe immune related adverse events were not increased with this combination strategy compared to historical data. This warrant further prospective analysis.