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

Area of Science:

• Oncology
• Genetics
• Vascular Biology

Background:

• Primary splenic angiosarcoma (PSA) is a rare and aggressive vascular cancer with limited treatment options and poor prognosis.
• Metastatic PSA presents significant challenges, often leading to treatment resistance and complications like hepatic failure and thrombocytopenia.

Purpose of the Study:

• To report the first use of inavolisib, a PI3Kα inhibitor, in combination with lenvatinib for treating refractory metastatic primary splenic angiosarcoma.
• To evaluate the efficacy and safety of this novel combination therapy in a patient with a specific PIK3CA mutation.

Main Methods:

• Genomic profiling of metastatic PSA identified a PIK3CA p.P471L missense mutation.
• A patient received sequential treatments including paclitaxel, liposomal doxorubicin, eribulin, toripalimab, and lenvatinib, with limited success.
• Treatment was switched to a combination regimen of inavolisib and lenvatinib.

Main Results:

• The combination of inavolisib and lenvatinib led to rapid normalization of bilirubin levels and recovery of platelet counts within two weeks.
• Follow-up MRI confirmed radiological stabilization of the disease.
• The patient remains alive and on treatment 16 months postdiagnosis, demonstrating significant clinical benefit.

Conclusions:

• This case demonstrates the potential efficacy of targeting the PI3K/AKT/mTOR pathway in PIK3CA-mutated angiosarcoma.
• Combined phosphoinositide 3-kinase and vascular endothelial growth factor pathway inhibition shows promise for refractory angiosarcoma.
• Early genomic profiling is crucial for identifying actionable mutations and guiding personalized treatment strategies in rare cancers like PSA.