Inavolisib and lenvatinib for PIK3CA-mutated refractory splenic angiosarcoma: a case report.

Primary splenic angiosarcoma (PSA) is a rare vascular malignancy with a poor prognosis and limited therapeutic options. A 62-year-old man with metastatic PSA underwent splenectomy followed by first-line paclitaxel, achieving stable disease for 7 months. Disease progression manifested as hepatic and bone marrow metastases with tumor-induced hepatic failure and refractory thrombocytopenia. Sequential treatment with liposomal doxorubicin, eribulin, toripalimab, and lenvatinib failed to control the disease failed to control the disease. Genomic profiling identified a PIK3CA p.P471L missense mutation. A combination regimen of inavolisib (a selective PI3Kα inhibitor) and lenvatinib was initiated. Bilirubin levels normalized, and platelet counts recovered within 2 weeks; follow-up MRI confirmed radiological stabilization. At 16 months postdiagnosis, the patient remains alive on this regimen, though long-term durability of response has yet to be determined. To our knowledge, this is the first reported use of inavolisib in angiosarcoma. The rapid biochemical and radiological response observed in this PIK3CA-mutated PSA supports early genomic profiling to identify actionable alterations and warrants prospective evaluation of combined phosphoinositide 3-kinase and vascular endothelial growth factor pathway inhibition in refractory angiosarcoma.