Denosumab administration in breast, prostate and lung cancer with chronic kidney disease – a retrospective multicenter Turkish Oncology Group (TOG) study

Background Denosumab, a RANK-ligand inhibitor, is an effectivetreatmentforfor bone metastasesfromsolidtumors.Unlikethebisphosphonates, it is not excretedbythekidney. Little is known, however, aboutitsefficacyandsafety in patientswith severe chronickidneydisease (CKD). Methods This study is a retrospective observational study and was conducted as a multicenter study within the scope of the Turkish Oncology Group (TOG) project. Patients with breast, prostate and lung cancer who received denosumab between January 2011 and December 2022.Datacollectedincludedinformationaboutthefollowing: CKD stage, fracturehistory, serum calciumlevelspreand post denosumabtreatment, episodes of hypocalcemia, relevantmedicationsand adverse events. Results A total of 262 patients from 17 centers were included in the study. Toxicitygrade ≥ 3 was seen in a total of 18 patients. Of these 18 patients, 16 had hypocalcemia and the others had eGFR decline. In 42 patients, eGFR was < 60 ml/min. Grade ≥ 3 toxicity (eGFR decrease in 2, hypocalcemia in 11) was detected in 13 of these patients and was statistically significant (p < 0.01).In 6 of 21 patients with pathologic fractures, GFR was < 60 ml/min, which was statistically significant (p = 0.035). In 6 of 21 patients with pathologic fractures, GFR was < 60 ml/min and was found to be statistically significant (p = 0.035). In 4 of 8 patients who underwent bone surgery for SRE, GFR was below 60 ml/min and was significant (p = 0.012). Conclusion A high rate of severe hypocalcemiawasobserved in patientswithadvanced CKD treatedwithdenosumab. Ifdenosumab is used in patientswith severe CKD, closemonitoringandaggressivereplacement of calciumandcalcitriol is requiredtoavoidthedevelopment of hypocalcemia.