Case report: Fournier’s gangrene occurring after inavolisib-induced hyperglycemia in a patient with metastatic breast cancer

Background Inavolisib is a selective inhibitor and degrader of mutant phosphatidylinositol 3-kinase alpha (PI3Kα) approved for PIK3CA -mutated, hormone receptor-positive, HER2-negative advanced breast cancer, and hyperglycemia is its most frequent class effect. Fournier’s gangrene is an uncommon necrotizing infection of the perineal region with reported mortality of 20%–40%. Necrotizing infections have only exceptionally been described in the context of PI3K inhibitor therapy, but to our knowledge Fournier’s gangrene has not been previously reported with any PI3Kα inhibitor. Case Summary A 57-year-old woman with PIK3CA -mutated metastatic breast carcinoma, obesity, and impaired fasting glucose without diabetes, receiving fulvestrant, palbociclib and inavolisib, developed grade 3 hyperglycemia refractory to metformin and rapid escalation of basal insulin, with a peak plasma glucose of 623 mg/dL. Inavolisib was interrupted and briefly reintroduced at a reduced dose, whereupon hyperglycemia recurred. Forty-seven days after inavolisib initiation, she was admitted to the intensive care unit with septic shock associated with necrosis of the skin over the perianal region and both buttocks. Contrast-enhanced computed tomography, polymicrobial cultures, and histology confirmed the diagnosis of Fournier’s gangrene. She required surgical debridements and fecal diversion, gradually recovering from the infection and undergoing reconstructive coverage of the gluteal defect. Eight months after presentation, the defect remained durably healed, while the metastatic breast cancer progressed and required two subsequent lines of systemic therapy. Conclusion This report describes the occurrence of inavolisib-induced hyperglycemia and a subsequent life-threatening necrotizing infection. Our findings support individualized metabolic and infectious risk stratification before PI3Kα inhibition and urgent evaluation of perineal symptoms in patients who develop severe or refractory hyperglycemia under these targeted therapies.