Acute proteinuric renal failure in a lung cancer patient treated with poziotinib: first case described in the literature

Introduction: The therapeutic approach to non-small cell lung cancer (NSCLC) has changed significantly in recent years: genomic drivers have enabled the development of new molecularly targeted therapies. The improvements obtained in the survival of these patients, the adverse events related to these novel treatments should not be forgotten. Poziotinib is a new generation tyrosine kinase inhibitor which has been recently registered for the treatment of patients with EGFR/HER2 exon 20 insertion mutation. Case Description: In 2017, a 58-year-old woman was diagnosed with a pT2, N2, M0, G2 NSCLC for which she was surgically treated with lobectomy and lymphadenectomy, followed by adjuvant CT; and after metastatic relapse, further CT until July 2020. Upon progression, she started Poziotinib. She was referred to us due to the occurrence of hypomagnesemia, hypokalemia and proteinuria (2.8 g/24 h), despite a normal renal function., The objective examination and blood tests were all normal, and the patient did not report any symptom. Due to a quick worsening of renal function (sCr 2 mg/dl), and in particular of proteinuria (3.3 g/24 h), Poziotinib was stopped and dexamethasone 4 mg/day was started. Examinations for glomerulopathies were not diriment; a renal biopsy was performed in order to guide therapeutic decisions. The histological picture showed incomplete glomerular sclerosis (5/15 glomeruli), outbreaks of tubulointerstitial sclero-atrophy, as well as interstitial inflammatory lymphoplasmacytic infiltrate; immunofluorescence was negative for all antisera, while electron microscopy is presently still in progress. Following the discontinuation of Poziotinib, a progressive improvement of AKI and a reduction of proteinuria (1.3 g/24 h) was observed, allowing to hold the drug accountable, in the absence of any other risk factor, for the renal AE observed. From a histological viewpoint, nephroangiosclerosis was documented, but steroidal therapy may have hidden peculiar glomerular lesions. Poziotinib wasn’t resumed. Discussion: This is the very first case of renal toxicity from Poziotinib treatment reported so far. Cases like this highlight the need for both a nephro-oncological evaluation as well as for dedicated paths to perform rapid renal biopsies in order to characterize these events and improve their management.