9,10 Tregs secrete cytokines to signal an upregulation of M2 tumor-associated macrophages. Regulatory T cells (Tregs), which play a key role in immunosuppression and increased tolerance to tumor cells, have also been observed in patients with endometrial cancer. 5-8 However, the prognostic significance of TILs has been conflicting. Tumor-infiltrating lymphocytes (TILs) have been observed in endometrial cancer, the association greater in cases with mismatch repair–deficient (dMMR) status. The endometrial tumor immune microenvironment is complex and dynamic. Within the gynecologic oncology space, immunotherapy has emerged as an effective treatment strategy for certain patients, with arguably the most dramatic effect in patients with endometrial cancer. These discoveries are helping to catalyze the investigation of anticancer therapies in a molecularly informed manner and, it is hoped, enrich responses to newly identified therapeutics. With the publication of The Cancer Genome Atlas, 4 distinct subclassifications of endometrial cancer emerged: DNA polymerase epsilon, catalytic subunit ( POLE)–mutated microsatellite instability–high (MSI-H) copy number–low and copy number–high. We now understand the relevance of molecular signature in potentially informing treatment outcomes. Historically, the treatment of patients with endometrial cancer has been risk-stratified by clinical and pathologic criteria alone. This notion of reduced sensitivity to cytotoxic chemotherapy in the recurrent setting was demonstrated in KEYNOTE-775, in which the median PFS for patients randomized to chemotherapy of physician’s choice was less than 4 months. 3 Importantly, however, GOG-209 required patients to be chemotherapy-naive, which calls into question the potential benefit of a combination platinum re-challenge in patients whose disease had progressed on prior systemic chemotherapy. 2 GOG-209 then demonstrated carboplatin and paclitaxel to be noninferior to cisplatin, doxorubicin, and paclitaxel, with less toxicity, ushering in an era in which carboplatin and paclitaxel became the preferred chemotherapy regimen for patients with advanced-stage or recurrent endometrial cancer. Despite improvements in progression-free survival (PFS) and overall survival (OS), this regimen was associated with significant treatment-related toxicity. 1 Given the rising incidence and mortality, with emerging data suggesting that endometrial cancer may overtake ovarian cancer as the most lethal gynecologic malignancy, there is a clear need to identify effective treatment options for patients with advanced-stage or metastatic disease.įollowing a series of clinical trials examining radiation therapy as well as single and doublet chemotherapy regimens, the GOG-177 trial from the Gynecologic Oncology Group identified cisplatin, doxorubicin, and paclitaxel as an effective triplet combination. Although most patients with endometrial cancer have localized disease, with a 5-year relative survival rate of 94.9%, patients with distant disease have a 5-year relative survival rate of approximately 18.4%. Given the recent advancements in immune oncology approaches, we review regimens approved by the US Food and Drug Administration as well as the interim results of ongoing phase 3 clinical trials.Įndometrial cancer is the most common gynecologic cancer in the United States. More recently, the identification of molecular subtypes has transformed the treatment paradigms for patients with endometrial cancer, especially in the immunotherapeutic arena. Traditionally, systemic treatment has included combination platinum- and taxane-based chemotherapy. Abstract: Endometrial cancer is the most common gynecologic cancer in the United States, with a rising incidence and mortality.
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