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Axitinib plus Immune Checkpoint Inhibitor: Evidence- and Expert-Based Consensus Recommendation for Treatment Optimisation and Management of Related Adverse Events - Beyond the Abstract

The treatment landscape in metastatic renal cell carcinoma (mRCC) has changed permanently in recent years. The dominance of tyrosine kinase inhibitors (TKI) as a single modality in first-line treatment of mRCC has vanished and combination therapies are currently considered a standard of care (SOC). The shift from single agents to combinations or dual-modality treatments improved the overall survival expectations in mRCC and combinations of ipilimumab and nivolumab, and axitinib in combination with either avelumab or pembrolizumab are novel SOC options in mRCC.

The checkpoint inhibitor backbone in these regimens is associated with immune-related adverse events (irAE), which overlaps with the TKI adverse event (AE) profile. This renders the dual-modality treatment of axitinib in combination with either avelumab or pembrolizumab of particular interest for therapy management. Dissecting immune-related from TKI-driven AEs is of critical interest in the clinic in order to trigger immune-suppressive or supportive measures to alleviate the symptom burden.

The article by Grünwald et al.1 represents a consensus approach for the management of axitinib and checkpoint inhibitor therapies. An expert panel reviewed current evidence and identified diarrhea, hepatitis, fatigue, and cardiovascular AEs as areas of unmet need in therapy management for such combinations. In a consensus approach, specifics for the management of axitinib in combination with avelumab or pembrolizumab were given. Alarming signs were identified, which should trigger immediate intervention. In contrast, clinical abnormalities that justify either withholding axitinib or corticosteroid use were acknowledged and specific therapy measures were recommended in order to improve patients' safety.

The expert consensus is thought to provide guidance for axitinib and checkpoint inhibitor combinations in the daily practice. It sets the boundaries to withhold therapy, add supportive measures or use of immune suppressants, thereby informing physicians about specific management of these particular combinations.

Written by: Viktor Grünwald, MD, Professor for interdisciplinary GU Oncology, University Hospital Essen (AöR), West-German Cancer Center Essen, Clinic for Medical Oncology and Clinic for Urology, Essen, Germany

Reference:

  1. Grünwald, Viktor, Martin H. Voss, Brian I. Rini, Thomas Powles, Laurence Albiges, Rachel H. Giles, and Eric Jonasch. "Axitinib plus immune checkpoint inhibitor: evidence-and expert-based consensus recommendation for treatment optimisation and management of related adverse events." British Journal of Cancer (2020): 1-7.
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