Quantifying the risk of hypocalcemia in individuals treated with cabozantinib.

Abstract

e24110 Background: Cabozantinib, a potent inhibitor for multiple receptor-tyrosine kinases, has been approved for the treatment of various advanced cancers. The risks of all-grade and high-grade hypocalcemia have been noted in many clinical trials. We have conducted an up-to-date systematic review and meta-analysis of clinical trials using single agent cabozantinib to assess the overall risk of hypocalcemia. Methods: We systematically identified relevant English-language studies primarily from PubMed and Clinicaltrials.gov (up to March 2023), covering phase I to phase III trials using cabozantinib in cancer patients. Studies with patients assigned to single agent cabozantinib with available data on hypocalcemia were included. We employed fixed-effects or random-effect models depending on study heterogeneity to calculate the incidence and relative risk of hypocalcemia. Results: A total of nineteen studies were included for analysis. The overall incidence of all-grade hypocalcemia with cabozantinib was 15.0% (95% CI: 9.0-21.0%), with a high-grade (grade 3 or 4) incidence of 2.0% (95% CI: 1.0-3.0%). Significant variability was observed among different tumor types (p < 0.001), ranging from 45.0% in multiple myeloma to 2.0% in hepatocellular carcinoma and colorectal cancer. In comparison with placebo, cabozantinib significantly increased the risk of hypocalcemia with an RR of 1.75 (95% CI: 0.96-2.53, p < 0.001). However, when compared to prednisone, cabozantinib showed a non-significant risk reduction of 0.30 (95% CI: -0.20-0.79, p = 0.24). Furthermore, cabozantinib did not elevate the risk of hypocalcemia compared to other chemotherapeutic agents (everolimus, paclitaxel, and sunitinib). Conclusions: Patients undergoing cabozantinib treatment face an increased risk of hypocalcemia, with variations observed across different tumor types. Proactive measures can be implemented to prevent or mitigate hypocalcemia during cabozantinib therapy. Additionally, monitoring vulnerable patient populations is essential to optimize clinical care and enhance overall outcomes.