The two antibodies belong to an emerging class of cancer immunotherapies, known as checkpoint inhibitors, which have shown high response rates and significant survival benefits in clinical trials.
Checkpoint inhibitors act at key checkpoints on the immune system, which tumour cells exploit to evade detection. Unlike chemotherapy and targeted anticancer agents, checkpoint inhibitors act indirectly by allowing the patient’s immune system to attack the tumour.
Nivolumab and pembrolizumab bind to the programmed death-1 (PD-1) receptor. Activation of PD-1 by tumour cells triggers an immune checkpoint, resulting in inhibition of T cells directed against the cancer antigens, preventing the immune system from attacking the tumour. Nivolumab and pembrolizumab block the PD-1 receptor, overriding the checkpoint and allowing T cells to kill the tumour cells.
Approval of nivolumab was based on data from two phase III studies, while three trials provided evidence to support the approval of pembrolizumab.
The most common adverse effects of nivolumab and pembrolizumab were fatigue, rash, pruritus, diarrhoea and nausea, most of which were mild to moderate. The most serious reactions were immune-related events (including pneumonitis, colitis, hepatitis, nephritis and endocrinopathies) and severe infusion-related reactions.