Afatinib-related kidney injury during treatment for EGFR-positive metastatic lung cancer

What happened, in summary

A 53-year-old Japanese man was diagnosed with stage IV EGFR-positive left lung adenocarcinoma after malignant cells were found in pleural effusion. He started afatinib 40 mg daily. During hospitalization for empyema, his kidney function deteriorated severely and he required three hemodialysis sessions. Because antibiotics were initially suspected, afatinib was restarted at 20 mg and later increased to 30 mg. After the dose increase, he developed fatigue, anorexia, nausea, a 7 kg weight loss, and recurrent severe kidney failure, with creatinine rising to 8.29 mg/dL. Afatinib was stopped again, and he required two more dialysis sessions. Kidney biopsy showed crescentic glomerulonephritis with limited vasculitis. He received intravenous methylprednisolone followed by oral prednisolone, and his kidney function partially recovered, although chronic impairment remained. Six months later, CT showed multiple lymph-node metastases. He began four monthly courses of carboplatin, paclitaxel, bevacizumab, and atezolizumab, followed by maintenance bevacizumab and atezolizumab every three weeks for five months. His renal function remained stable enough to continue the second-line regimen. The treatment course required permanent discontinuation of afatinib and a change from EGFR-targeted therapy to combination chemotherapy, anti-angiogenic therapy, and immunotherapy.