Should MMMT of the endometrium/ovary be treated with anthracycline instead of taxane based chemotherapy?

Abstract

5563 Background: Carcinosarcomas of endometrial (MMMT-E) and ovarian (MMMT-O) origin are rare biphasic tumors, associated with poor prognosis and thought to be epithelial in origin. In view of this, there has been a shift towards carboplatin and paclitaxel rather than anthracycline based chemotherapy regimens which were used when they were treated as “sarcomas”. The purpose of this large retrospective study is to determine whether this change in chemotherapy is associated with better outcomes. Methods: Firstly, clinicopathological features of patients with all stages of MMMT-E (n=103) and -O (n=17) were compared to patients with adenocarcinoma of the endometrium (n=172) and ovary (n=189) in a case-controlled study. Clinicopathological characteristics, FIGO stage, first-line regimens and patient outcomes were analyzed. Secondly, primary tumor specimens of high grade serous ovarian cancers (HGSOC, n=1290) and MMMT-O (n=450) from an independent cohort were analyzed using immunohistochemistry and next generation sequencing to predict response to chemotherapeutic agents. Results: MMMT have a poor prognosis, however, there was a plateau in survival of MMMT-E after 2.5 years in patients with FIGO stage I/II disease, with no recurrence/cancer deaths observed beyond this. There was a statistically significant worse relapse-free survival in patients with MMMT-E treated with carboplatin and paclitaxel compared to carboplatin and anthracyclines (p=0.0011). In the second independent prospective cohort comparing HGSOC versus MMMT-O, both were driven predominantly by p53 mutations. MMMT-O expressed statistically more commonly PI3KCA and KRAS (p=0.015 and 0.018), respectively. Of particular interest, both HGSOC and MMMT-O showed a higher percentage of probability of responding to a combination of carboplatin/anthracyclins (71.2 vs. 73.9%) than carboplatin/taxanes (58.4 vs 39.4%). Conclusions: Patients with MMMT-E and stage I/II have an excellent prognosis if there is no recurrence by 2.5 years. Platinum/anthracyclines regimens appear to be associated with a better outcome than platinum/taxane in MMMT-E and MMMT-O. This could be tested in an international prospective randomized controlled trial.