Investigating the side effect profiles of different PD-L1/PD-1 inhibitor-based combination therapies.

This study investigated the side effect profiles of different PD-1/PD-L1 inhibitor-based combination therapies. The data showed that PD-1/PD-L1 inhibitors in combination with chemotherapy were associated with a higher risk of treatment-related side effects than with targeted therapy or immunotherapy combinations.

Immunotherapy uses the body’s own system to fight cancer. Tumor cells try to avoid death by switching off our immune system. They bind to proteins on the surface of the immune cells such as PD-1/PD-L1. These proteins can stop the immune system from killing cancerous cells. Pembrolizumab (Keytruda) and nivolumab (Opdivo) are examples of PD-1 and PD-L1 inhibitors that work by blocking PD-1/PD-L1. This inhibition triggers the immune system to attack tumor cells and kills them.

PD-1/PD-L1 inhibitors in combination with other therapies such as chemotherapy, targeted therapy, and radiotherapy have shown to significantly improve the outcomes of patients with many types of advanced cancers. However, there are very few studies analyzing the treatment-related side effects associated with different PD-1/PD-L1 inhibitor-based combination therapies.

This study investigated 161 studies and involved 17,197 patients treated with PD-1/PD-L1 inhibitor-based combination therapies. Studies were divided into 4 groups based on the combination strategy used. Group 1 included 44 studies with PD-1/PD-L1 inhibitors combined with chemotherapy. Group 2 included 51 studies with PD-1/PD-L1 inhibitors combined with targeted therapy. Group 3 included 58 studies with PD-1/PD-L1 inhibitors combined with immunotherapy. Group 4 included studies with PD-1/PD-L1 inhibitors combined with radiotherapy.

For group 1, 97.7% of patients experienced treatment-related side effects and 68.3% experienced severe side effects. For group 2, 94.5% of patients experienced treatment-related side effects and 47.3% experienced severe side effects. For group 3, 86.8% of patients experienced treatment-related side effects and 35.9% experienced severe side effects. For group 4, 89.4% of patients experienced treatment-related side effects and 12.4% experienced severe side effects.

The most common side effects were low red blood cell counts (45.4%) and hair loss (45.1%) for group 1. The most common side effects for group 2 were fatigue (34.3%) and diarrhea (31.7%). In group 3, the most common side effects were also fatigue (26.4%) and diarrhea (21.1%). For group 4, the most common side effects were problems with swallowing (30%) and nausea (24.9%).

The most common severe side effects for group 1 were low white blood cell counts (19.6%) and low red cell counts (11.4%). For group 2, the most common severe side effects were high blood pressure (9.3%) and low potassium levels (3.6%). For group 3, the most common severe side effects were increased pancreatic enzymes (7.2%) and inflammation of the lining of the colon (3.6%). For group 4, the most common severe side effects were low white blood cell counts (10.3%) and problems swallowing (8.8%).

This study concluded that PD-1/PD-L1 inhibitors in combination with chemotherapy were associated with a higher risk of treatment-related side effects than with targeted therapy or immunotherapy combinations.

The definitions of treatment-related side effects were not very clear in a few studies. Larger real-world studies are needed to validate the findings. The number of studies analyzed for the radiotherapy combination group was very small and no randomized controlled trials were included.