To perform comprehensive molecular profiling (CGP) on a large cohort of patients with uterine carcinosarcomas to identify potential therapeutic targets.
Uterine carcinosarcomas—also known as malignant mixed mesodermal tumors (MMMTs)—comprise only 5% of uterine cancers, yet account for disproportionately more uterine cancer-related deaths owing to their aggressive behavior. Uterine carcinosarcomas present with extrauterine disease in 60% of patients. In patients with early-stage disease (I or II) who receive adjuvant treatment, recurrence rates approach 50%(1).
In advanced stages of disease, the mainstay of treatment remains chemotherapy but cure rates are suboptimal. In a series of 121 patients with uterine carcinosarcomas, five-year stage-specific survival rates were 59, 22, and 9 percent for women with stage I/II, III, or IV disease, respectively(2). Standard treatment options are inadequate, and studies attempting to identify more effective agents have been disappointing.
More research is needed to elucidate the aggressive nature of these cancers, as well as identify treatment targets. More research is needed to elucidate the aggressive nature of these cancers, as well as identify treatment targets.
To our knowledge, this is the largest cohort of uterine MMMTs to be molecularly profiled. Multiple somatic mutations and copynumber alterations in genes that are therapeutic targets were identified. Our data suggests CGP may inform treatment, for example, targeting the PI3K/AKT pathway with mTOR inhibition, chromatin remodeling therapies including EZH2 or PARP inhibition, or VEGF inhibition. PD-1/PD-L1 inhibition may be useful in a subset of patients with high TML/MS instability. Clinical trials are needed to validate these observations.Download Publication