Pembrolizumab and Bevacizumab Classification
Pembrolizumab is an immunotherapy agent (specifically a PD-1 immune checkpoint inhibitor), while bevacizumab is a targeted therapy (specifically an anti-VEGF monoclonal antibody). 1, 2
Pembrolizumab: Immunotherapy Mechanism
Pembrolizumab functions as an immune checkpoint inhibitor by blocking the PD-1 receptor on T cells. 1 The drug works through the following mechanism:
- Pembrolizumab is a humanized monoclonal IgG4 antibody that binds to the PD-1 receptor found on T cells 1
- It blocks the interaction between PD-1 and its ligands (PD-L1 and PD-L2), which normally inhibit T cell proliferation and cytokine production 1
- By releasing this PD-1 pathway-mediated inhibition, pembrolizumab restores the anti-tumor immune response 1
- This mechanism classifies pembrolizumab definitively as immunotherapy, as it enhances the patient's own immune system to fight cancer 3, 4
The Society for Immunotherapy of Cancer explicitly categorizes pembrolizumab as an immune checkpoint inhibitor (ICI) in their clinical practice guidelines for multiple cancer types. 3
Bevacizumab: Targeted Therapy Mechanism
Bevacizumab is a targeted therapy that specifically inhibits vascular endothelial growth factor (VEGF-A). 2 The drug works through the following mechanism:
- Bevacizumab is a VEGF-A-targeting monoclonal antibody that blocks angiogenesis (blood vessel formation) in tumors 2
- It was one of the first approved angiogenesis inhibitors and remains the most extensively characterized anti-angiogenetic treatment 2
- The drug directly targets a specific molecular pathway (VEGF signaling) rather than modulating the immune system 2
- This mechanism classifies bevacizumab as targeted therapy, not immunotherapy 3, 5
Clinical Context: Combination Therapy
These two agents are frequently combined in cancer treatment because they work through complementary mechanisms. 3, 5 Important clinical considerations include:
- In cervical cancer, pembrolizumab is FDA-approved in combination with platinum-based chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic PD-L1-positive (CPS≥1) disease 3, 5
- The KEYNOTE-826 trial demonstrated that adding pembrolizumab to chemotherapy ± bevacizumab improved progression-free survival (10.4 vs 8.2 months, HR 0.62) and overall survival in cervical cancer 3, 5
- VEGF not only controls blood vessel formation but also modulates tumor-induced immunosuppression, which provides rationale for combining bevacizumab with immunotherapy 2
- Recent evidence shows that bevacizumab can transform tumors with low immunoreactivity into "hot" tumors by increasing CD8+ cytotoxic T cell infiltration through vascular normalization 6
A common pitfall is assuming that all monoclonal antibodies used in cancer are immunotherapy—this is incorrect. Bevacizumab targets a growth factor pathway (VEGF), not the immune system, making it targeted therapy despite being an antibody. 2 Only antibodies that modulate immune checkpoints (like pembrolizumab targeting PD-1) or directly engage immune cells are classified as immunotherapy. 3, 4