Should MMMT still be treated with adjuvant taxane-based combination chemotherapy?

ABSTRACT: BACKGROUND:Malignant mixed Mullerian tumors of endometrial (MMMT-E) and ovarian (MMMT-O) origin are associated with poor prognosis. Suggestively epithelial-driven tumors, their treatment has shifted from anthracycline or ifosfamide-based towards taxane-based chemotherapy. It remains unclear whether this change associates with better outcomes. PATIENTS AND METHODS:A conjoined Australian and Swiss patient cohort of MMMT-E (N?=?103) and MMMT-O (N?=?17) was compared to patients with adenocarcinoma of the endometrium (EC, N?=?172) and ovary (OC, N?=?189). Clinicopathological characteristics, FIGO stage, first-line treatment, and patient outcomes were analyzed. The generated hypothesis was verified in an US-American cohort with high-grade serous ovarian cancer (HGSOC, N?=?1290) and MMMT-O (N?=?450) using immunohistochemistry and next-generation sequencing. RESULTS:Early stage I/II MMMT-E showed a survival plateau after 2.5 years, with no recurrence or death observed afterwards. Relapse-free survival was significantly worse in MMMT-E treated with platinum/taxanes (P?=?0.024) compared to non-taxane regimen. Hypothesizing that also MMMT-O might benefit from an adjuvant non-paclitaxel regimen, a second independent cohort of MMMT-O and HGSOC patients was examined. p53 mutations dominated in both cancers with comparable frequency. PI3KCA and KRAS mutations were less frequent: they were more frequent in MMMT-O than in HGSOC (P?=?0.015 and P?=?0.018, respectively). MMMT-O responded better to a combination of carboplatin with anthracyclines than with taxanes (73.9% vs. 39.4%). CONCLUSION:Early stage I/II MMMT-E patients have excellent prognosis if no recurrence has appeared within the first 2.5 years. In MMMT-E, platinum/anthracycline or ifosfamide regimen associated with better outcomes than platinum/taxanes regimens. This might also apply to MMMT-O.

SUBMITTER: Heinzelmann-Schwarz V 

PROVIDER: S-EPMC7039840 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature