Evaluating the risk of cardiovascular side effects in cancer patients treated with PD-1/PD-L1 inhibitors.

This study evaluated the risk of cardiovascular (CV; heart and blood vessels) side effects in cancer patients treated with PD-1/PD-L1 inhibitors. The data showed that PD-1/PD-L1 inhibitors alone or combined with chemotherapy significantly increased the risk of CV side effects. PD-1/PD-L1 inhibitors combined with chemotherapy significantly increased the risk of irregular heartbeat and hypertension (high blood pressure).

Immunotherapy uses the body’s own system to fight cancer and has been found to be effective in many types of cancer including melanoma, lung cancer, and breast 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 or CTLA-4.  

Immune checkpoint inhibitors (ICI) such as pembrolizumab (Keytruda) and ipilimumab (Yervoy) block these interactions and turn on the immune system to attack and kill the cancer cells. PD-1/PD-L1 and CTLA-4 inhibitors as first-line treatments have been found to significantly improve the outcomes of patients with advanced non-small lung cancer (NSCLC). The most common side effects associated with immunotherapy are immune-related. These events often include skin rashes or inflammation in areas such as the lungs, intestines, or thyroid.

PD-1/PD-L1 inhibitors have also been associated with cardiovascular (CV; heart and blood vessels) side effects. However, whether PD-1/PD-L1 inhibitors treatment increases the risk of CV side effects in patients with cancer is still unclear.

This study analyzed 50 studies and involved cancer patients who experienced CV side effects. The studies compared one of these treatments- PD-1/PD-L1 inhibitors alone to placebo/chemotherapy, PD-1/PD-L1 inhibitors combined with chemotherapy to chemotherapy, or PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors to ICIs alone.

PD-1/PD-L1 inhibitors alone significantly increased the risk of CV side effects by 2.11 times compared with a placebo. However, there was not an increased risk of severe CV side effects with PD-1/PD-L1 compared to placebo.

PD-1/PD-L1 inhibitors alone slightly increased the risk of CV side effects by 26% compared to chemotherapy. PD-1/PD-L1 inhibitors alone slightly increased the risk of severe CV side effects by 52% compared to chemotherapy.

PD-1/PDL1 inhibitors combined with chemotherapy significantly increased the risk of CV side effects by 1.53 times and significantly increased the risk of severe CV side effects by 1.63 times compared with chemotherapy alone.

PD-1/PD-L1 inhibitors alone did not significantly increase the risk of inflammation of the heart muscle, irregular heartbeat, and hypertension compared with placebo or chemotherapy. PD-1/PD-L1 inhibitors combined with chemotherapy significantly increased the risk of irregular heartbeat by 1.63 times, hypertension by 1.34 times, and severe hypertension by 1.54 times compared with chemotherapy alone.

This study concluded that PD-1/PD-L1 inhibitors alone or combined with chemotherapy significantly increased the risk of CV side effects. PD-1/PD-L1 inhibitors combined with chemotherapy significantly increased the risk of irregular heartbeat and hypertension.

This study looked back in time at medical records. This study analyzed data from clinical trials which did not include factors such as the previous treatment of patients. Some studies analyzed in this study only included risks for high or severe cardiovascular side effects which might affect the conclusions.