Is dexamethasone (corticosteroid) premedication recommended before durvalumab (monoclonal antibody) infusion?

Dexamethasone Premedication Before Durvalumab

Premedication with dexamethasone is not recommended before durvalumab infusion as durvalumab has a low incidence of infusion reactions and routine premedication may unnecessarily expose patients to corticosteroid side effects. 1

Infusion Reaction Risk with Durvalumab

• Durvalumab is classified as having low emetogenic potential (10-30%), which does not require routine prophylaxis with dexamethasone 1
• The incidence of infusion reactions with PD-1/PD-L1 pathway inhibitors like durvalumab is very low (<1% of adverse events in phase III studies) 1
• In the PACIFIC trial, which established durvalumab as standard of care in stage III NSCLC, immune-mediated adverse events occurred in approximately 25% of patients, but only 3.4% experienced grade 3/4 events, indicating a generally favorable safety profile 2

Guidelines for Premedication with Immune Checkpoint Inhibitors

• According to ESMO Clinical Practice Guidelines, premedication is not recommended for anti-PD-L1 agents like durvalumab [IV, B] 1
• Unlike other monoclonal antibodies such as cetuximab (which requires corticosteroid premedication) or daratumumab (which requires methylprednisolone premedication), durvalumab does not have a high risk of infusion reactions that would necessitate routine premedication 1
• For comparison, atezolizumab (another anti-PD-L1 agent) also has a recommendation against routine premedication [IV, B] 1

Management of Infusion Reactions if They Occur

• If an infusion reaction does occur with durvalumab, the recommended approach is:
  • Grade 1/2: Stop or slow the infusion rate and provide symptomatic treatment 1
  • Grade 3/4: Stop the infusion, provide aggressive symptomatic treatment, and permanently discontinue durvalumab 1
• After experiencing an infusion reaction, premedication with antipyretics and antihistamines may be considered for subsequent infusions, similar to the approach with nivolumab 1

Corticosteroids and Immune Checkpoint Inhibitors

• There has been historical concern that prophylactic corticosteroids might compromise the anti-tumor efficacy of immune checkpoint inhibitors 3
• Recent research suggests that corticosteroid premedication does not significantly compromise anti-tumor efficacy of dual immune checkpoint blockade in murine models 3
• However, without a clear benefit in preventing infusion reactions with durvalumab, exposing patients to unnecessary corticosteroids is not recommended 1

Special Considerations

• If durvalumab is being administered in combination with chemotherapy that requires dexamethasone premedication, the dexamethasone would be given as part of the chemotherapy regimen, not specifically for durvalumab 1
• For patients with a history of severe allergic reactions to other medications or previous infusion reactions, individual risk assessment may be warranted, but routine premedication is still not recommended based on current guidelines 1

Common Pitfalls to Avoid

• Avoid unnecessary premedication with corticosteroids as this may expose patients to steroid-related side effects without clear benefit 1, 4
• Do not confuse durvalumab with other monoclonal antibodies that do require premedication, such as cetuximab or daratumumab 1
• Remember that if a patient experiences an infusion reaction with durvalumab, subsequent infusions may benefit from premedication, but this is not needed for initial treatment 1