durvalumab
Summary
Durvalumab is a human IgG1 monoclonal antibody that inhibits PD-L1, blocking its interaction with PD-1 and B7.1, thereby restoring T-cell mediated antitumor immunity. It is FDA-approved for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy, extensive-stage small cell lung cancer, and biliary tract/hepatocellular carcinoma in combination regimens. Key toxicities are immune-related adverse events (irAEs) due to loss of peripheral tolerance.
Detail
Durvalumab targets programmed death-ligand 1 (PD-L1), a checkpoint molecule expressed on tumor cells and antigen-presenting cells. Normally, PD-L1 binding to PD-1 on T cells delivers an inhibitory signal that dampens T-cell activation, allowing tumors to evade immune surveillance. By blocking PD-L1, durvalumab prevents this inhibitory signal, unleashing cytotoxic T-cell activity against tumor cells (checkpoint inhibition).
Clinical use: Durvalumab is approved for consolidation therapy in unresectable stage III NSCLC following concurrent chemoradiation (PACIFIC trial showed improved progression-free and overall survival), for extensive-stage small cell lung cancer in combination with platinum-etoposide chemotherapy, and for biliary tract cancer and hepatocellular carcinoma in combination with chemotherapy or other agents (e.g., tremelimumab, an anti-CTLA-4 antibody).
Mechanism-related adverse effects: Because checkpoint inhibitors remove a natural brake on the immune system, they can cause immune-related adverse events (irAEs) affecting multiple organ systems: pneumonitis, colitis, hepatitis, endocrinopathies (thyroiditis, adrenal insufficiency, hypophysitis, type 1 diabetes), dermatitis, and rarely myocarditis. These are managed with corticosteroids and, in severe cases, discontinuation of therapy.
High-yield boards points: Recognize durvalumab as a PD-L1 inhibitor (distinguish from PD-1 inhibitors like nivolumab/pembrolizumab and CTLA-4 inhibitors like ipilimumab). Understand the general class effect of irAEs and their management. Know its role in NSCLC consolidation therapy post-chemoradiation as a testable clinical scenario.
Sources
- First Aid for the USMLE Step 1
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- PACIFIC Trial (NEJM 2017)
- UpToDate: Immune checkpoint inhibitors
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.