Ossifying fibromyxoid tumor with a novel PIK3CA mutation (c.1624G>A) unresponsive to alpelisib: A case report

Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal tumor of uncertain origin, and the biological course of common OFMTs is indolent. Gene fusion constitutes an important pathogenic event in the development of OFMT, and recurrent PHF1 gene rearrangements are detected in up to 80 % of OFMTs. Here, we report a case of a 35-year-old man with elbow OFMT that recurred and metastasized to lung. Comprehensive genomic profiling by next-generation sequencing (NGS) at the time of recurrence identified a rare mutation in PIK3CA. Based on the findings, the patient opted for off-label therapy with alpelisib, an α-specific PI3K inhibitor that selectively targets p110α and has shown promising efficacy in breast cancer patients harboring the identical PIK3CA mutations. However, no clinical response was observed in the patient, and the lack of response may be associated with the specific nature of the PIK3CA mutation, and/or other unfavorable tumor biological factors that override any benefit from alpelisib.