FDA-Approved Immunotherapy Drugs for Cancer Treatment
Multiple FDA-approved immunotherapy drugs are currently available for cancer treatment, with immune checkpoint inhibitors representing the dominant class, including PD-1 inhibitors (nivolumab, pembrolizumab, cemiplimab), PD-L1 inhibitors (atezolizumab, durvalumab, avelumab), CTLA-4 inhibitor (ipilimumab), and LAG-3 inhibitor (relatlimab).
Immune Checkpoint Inhibitors
The FDA has approved eight immune checkpoint inhibitors that work by blocking self-tolerance pathways exploited by tumors 1, 2:
PD-1 Inhibitors
- Nivolumab - First approved in 2015 for advanced renal cell carcinoma after prior anti-angiogenic therapy 3; also approved for NSCLC 1
- Pembrolizumab - Approved for NSCLC and in combination with axitinib for first-line treatment of advanced RCC 3
- Cemiplimab - Approved for various cancer indications 2, 4, 5
PD-L1 Inhibitors
- Atezolizumab - Approved for NSCLC 1
- Durvalumab - Approved for NSCLC 1
- Avelumab - Approved in combination with axitinib for first-line treatment of advanced RCC (May 2019) 3
CTLA-4 Inhibitor
- Ipilimumab - Approved in combination with nivolumab for intermediate- and poor-risk, previously untreated advanced RCC (April 2018) 3
LAG-3 Inhibitor
- Relatlimab - The newest class of immune checkpoint inhibitor 2
Combination Immunotherapy Regimens
The FDA has approved several combination strategies that demonstrate superior outcomes compared to monotherapy:
- Nivolumab + Ipilimumab for intermediate/poor-risk advanced RCC 3
- Pembrolizumab + Axitinib for first-line advanced RCC 3
- Avelumab + Axitinib for first-line advanced RCC 3
These combination regimens represent a paradigm shift, particularly in renal cell carcinoma where they have replaced traditional VEGF-targeting monotherapy as first-line options.
Other Immunotherapy Modalities
Beyond checkpoint inhibitors, additional FDA-approved immunotherapy approaches include 6, 7:
- Oncolytic viruses (OVs)
- Cytokines
- Cancer vaccines
- Chimeric antigen receptor T-cell (CAR-T) therapy
- Monoclonal antibody-drug conjugates (e.g., Enhertu, Elahere) 8
Cancer-Specific Applications
The approved immunotherapies have demonstrated efficacy across multiple cancer types 4, 5:
- Melanoma
- Non-small cell lung carcinoma
- Renal cell carcinoma
- Breast cancer
- Hepatocellular carcinoma
- Hodgkin lymphoma
- Cervical cancer
- Head and neck squamous cell carcinoma
- Bladder cancer
Critical Implementation Considerations
PD-L1 biomarker testing has been approved as a companion/complementary diagnostic to guide patient selection, though significant variability exists in assay systems, tissue processing, and cutoff values that complicate interpretation 1. This represents a common pitfall—do not rely solely on PD-L1 expression as some patients without PD-L1 expression still respond to therapy.
The rapid adoption of immunotherapy from first objective response in 2012 to FDA approval in 2015 for NSCLC underscores the transformative nature of these agents 1. However, not all patients respond favorably, necessitating consideration of additional biomarkers including tumor mutation burden (TMB), microbiome composition, hypoxia markers, and interferon-γ levels 5.
Immune-related adverse events (irAEs) represent a distinct toxicity profile requiring specialized monitoring and management protocols, as these agents modulate T-cell function and can cause autoimmune-like reactions across multiple organ systems 1, 2, 4.