![]() In this study, there was close to 50% response rate. These are patients whose progression-free survival is very short. These are patients who can’t be cured or haven’t been able to be cured. More important, we’re talking about recurrent metastatic endometrial cancer, which has already been treated with chemotherapy. If you look at a summary of the endometrial portion of KEYNOTE-158-and Dave O’Malley’s paper, a great summary in the Journal of Clinical Oncology-demonstrated that in MSI –high endometrial cancers, response rate was close to 50%. The fact that the FDA eventually approved the drug based on that tells you how dramatic the results were. It was a basket trial, so these aren’t randomized prospective phase 3 trials. There were 2 cohorts, D and K, that had endometrial cancers in there, and many had mismatch repair abnormalities. It was essentially designed across many tumors, not just endometrial cancer. The classic trial for this tumor is KEYNOTE-158, which was a basket trial. It evolved while the trials were ongoing, but it made a lot of sense. That’s why we see such dramatic responses in these types of tumors to those agents. A drug like pembrolizumab, which activates T cells by inhibiting that pathway, anti–PD-1, will activate all these T cells, which will then fight the tumor. And the tumors are clever, so they begin to put the T cells asleep, if you will, through a number of mechanisms, including PD-1. These mismatch repair–abnormal tumors are loaded with new proteins that the body recognizes as foreign. This results in the slipping of DNA as it gets replicated so that you add an extra base here and there, which then produces an abnormal protein that the body hasn’t seen. Michael Birrer, MD, PhD: There’s a rationale for the use of immuno-oncology drugs like pembrolizumab in tumors that have a DNA-repair abnormality, particularly if the DNA-repair abnormality is mismatch repair. 15 months later the patient has disease relapse with metastases to the paraaortic lymph nodes. ![]() She then was treated with carboplatin/paclitaxel chemotherapy which was well tolerated.12 months after completing radiotherapy, she presented with new RLE edema and right hydroureter.Postoperative radiotherapy: vaginal cuff brachytherapy to a dose of 21 Gy in 3 fractions.Molecular testing shows MSI-high, MMR proficient, and HER2.Pathology: grade 2 endometrioid adenocarcinoma, 15 negative pelvic nodes, invasive 1.9 cm of 2.4 cm myometrium.Surgery: ELAP TAH BSO with bilateral pelvic node dissection.Endometrial biopsy: endometrioid adenocarcinoma, FIGO grade 1.PE: Notable for large uterus and tenderness upon palpation.She has a grown daughter, underwent menopause at 52 years of age, and her father had prostate cancer in his late 60’s. A 70-year-old postmenopausal woman presents after experiencing abnormal uterine bleeding for about 3 months.Case: A 70-Year-Old Woman With Endometrial Cancer
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