Renal Safety Profile of EGFR Targeted Therapies: A Study from VigiBase(R) the WHO Global Database of Individual Case Safety Reports

Simple Summary Drugs targeting the epithelial growth factor receptor (EGFR) are used in pulmonary and digestive cancers and represent major medical progress. In addition to its localization in cancer cells, EGFR can also be found in the kidney. This observation raises the question of the renal toxicity of these drugs. This issue has been addressed in the present study conducted on safety data from the largest international pharmacovigilance database, VigiBase(R). This study showed that the renal toxicity of these drugs is mainly represented by renal failure in the context of digestive toxicity. A new adverse effect called haemolytic and uremic syndrome or thrombotic microangiopathy has been found for erlotinib, which is the first anti-EGFR drug to obtain market authorisation. This signal has to be confirmed. No other renal toxicity has been found related to anti-EGFR drugs, in particular, neither glomerular nor tubular toxicity. Kidney EGFR expression together with reported cases of glomerular diseases in the context of anti-EGFR drug administration raise concerns about the renal safety profile of these drugs. This issue is addressed in a case/non-case study carried out on VigiBase(R), the WHO global database of individual case safety reports (ICRS). Disproportionality analysis of renal adverse effects related to the selected anti-EGFR drugs, erlotinib, gefitinib, afatinib, osimertinib, cetuximab and panitumumab, was assessed using the reporting odds ratio (ROR). Nine hundred and eighty-nine ICRSs were included. A signal of disproportionate reporting (SDR) was found for afatinib (ROR = 2.70; 95% CI [2.22-3.29]) and erlotinib (ROR = 1.73; 95% CI [1.46-2.04]) with acute kidney injury, and for afatinib (ROR = 2.41; 95% CI [1.78-3.27]), cetuximab (ROR = 1.42; 95% CI [1.14-1.78]) and erlotinib (ROR = 2.23; 95% CI [1.80-2.77]) with renal failure. The preferred term diarrhoea was frequently reported in the included cases. An SDR was found for erlotinib with haemolytic and uremic syndrome (ROR = 4.01; 95% CI [1.80-8.94]) and thrombotic microangiopathy (ROR = 4.94; 95% CI [2.80-8.72]). No SDR was seen for glomerular or tubule-interstitial diseases. This study showed that the anti-EGFR drug renal toxicity is mainly related to renal failure in the context of digestive toxicity.

Automated summary

This study found that the renal toxicity of anti-EGFR drugs is primarily related to renal failure in the context of digestive toxicity. Signals of disproportionate reporting were observed for afatinib and erlotinib with acute kidney injury, and for afatinib, cetuximab, and erlotinib with renal failure. Additionally, erlotinib was associated with haemolytic and uremic syndrome and thrombotic microangiopathy.