A novel premedication strategy has shown promising results in reducing infusion-related reactions (IRRs) for amivantamab, a targeted therapy used in non-small cell lung cancer (NSCLC) treatment. The SKIPPirr trial investigated an enhanced premedication protocol that dramatically decreased IRR incidence from 67% observed in the CHRYSALIS study to 22.5%.
Enhanced Premedication Protocol Shows Significant Efficacy
The SKIPPirr trial's enhanced premedication protocol represents a substantial advancement in managing one of amivantamab's most challenging adverse effects. The protocol includes dexamethasone 8 mg administered twice daily for two days prior to infusion, followed by dexamethasone 8 mg given one hour before infusion, combined with standard premedications including diphenhydramine and acetaminophen.
This approach addresses the high IRR incidence that has been a significant concern with amivantamab therapy. The original CHRYSALIS study reported IRRs in 67% of patients, making effective prophylaxis a critical clinical need.
Standard Management Approaches for NSCLC Infusion Reactions
Healthcare institutions are recommended to develop comprehensive hypersensitivity guidelines for common NSCLC treatment agents, including platinum agents, taxanes, monoclonal antibodies, and immunotherapy agents. In the absence of institutional protocols, package inserts provide essential guidance on required premedications, management of reactions by grade and severity, and recommendations for subsequent dosing.
The standard premedication strategy employs a dual histamine blockade approach using H1 antagonists such as diphenhydramine or cetirizine, combined with H2 antagonists like famotidine, along with corticosteroids.
Adaptive Strategies for Managing Future Infusions
Following an IRR, several considerations guide treatment decisions for subsequent infusions. A step titration method may be introduced, and additional premedications may be considered based on the patient's response. For patients susceptible to anticholinergic adverse effects, cetirizine can replace diphenhydramine as the H1 antagonist. Montelukast may also be used for pretreatment at home in certain cases.
Key clinical decisions following IRRs include determining whether to restart the current infusion after reaction resolution, which requires both physician and patient agreement, and modifying premedication approaches for subsequent infusions.
Current Research Challenges in NSCLC Management
The field faces several critical gaps that highlight the importance of advances like improved IRR management. In early-stage NSCLC, multiple FDA approvals for neoadjuvant and adjuvant chemoimmunotherapy have been granted, but mature data is still needed to establish the optimal treatment approach.
Tumor heterogeneity presents another significant challenge, with multiple targetable mutations often present in individual patients. Currently, no data exists on combining targeted therapies to address this complexity. Additionally, research is needed to understand mechanisms of immunotherapy nonresponse and identify additional therapeutic targets for patients who do not respond to current immunotherapy approaches.
The focus remains on minimizing toxicity exposure when treatment benefit cannot be guaranteed, making advances in supportive care measures like enhanced premedication protocols particularly valuable for improving patient outcomes and treatment tolerability.
