Significant benefit of everolimus in a patient with urothelial bladder cancer harboring a rare M1043I mutation of PIK3CA.

Urothelial bladder cancer (UBC) is a common malignancy with considerable mortality worldwide. However, the treatment options of UBC are mainly chemotherapy and immunotherapy, as few targeted agents have demonstrated efficacy against UBC. In recent studies, everolimus has exhibited antitumor activity in patients harboring aberrations in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathway in multiple tumor types. Herein, we report the case of a patient with metastatic UBC harboring a rare M1043I mutation of PIK3CA which was detected using DNA-based next-generation sequencing. The patient received everolimus as first-line therapy after palliative transurethral resection. The treatment resulted in complete response within 1 month, and the patient achieved a progression-free survival (PFS) of >6 months according to reports from the last follow-up visit. To our knowledge, this is the first reported case of PIK3CA-mutant UBC for which everolimus therapy demonstrated a significant benefit suggesting that the rare M1043I mutation variant may be a potential biomarker of sensitivity to everolimus. Further insights into its mechanism and clinical studies are needed to clarify the effectiveness of everolimus therapy in patients with PIK3CA M1043I mutation.