![]() Preclinical data suggested that antiangiogenesis agents might reduce VEGF-mediated immune suppression and thus potentially synergize with immunotherapy agents. These data led to the approval of pembrolizumab for patients with MSI-H tumors, which includes nearly 25% of those with endometrial cancer.īuilding off these remarkable responses, investigators examined whether the addition of other agents to pembrolizumab could achieve for microsatellite-stable (MSS) tumors the same results as these initial findings. Treatment-related grade 3 or 4 adverse events were reported in just 14.7% of patients in the study. This type of durability implies both efficacy and reasonable tolerance. ![]() Median overall survival was also dramatic-22.7 months (95% CI = 2.5 months to not reached). 3 The response rate in this group of patients was a startling 57% (95% confidence interval = 42.2%–71.2%). KEYNOTE-158 examined the use of the anti–PD-1 antibody pembrolizumab in microsatellite instability–high (MSI-H) tumors, including 49 women with endometrial cancer. The remarkable finding that microsatellite instability could be exploited to induce an immune response by checkpoint inhibitors was just such a change. A radical shift in cancer treatment was clearly needed for this disease. Agents such as bevacizumab, everolimus plus letrozole, and tamoxifen plus megestrol acetate have demonstrated varying efficacy, but durable responses are uncommon. Single-agent chemotherapy with doxorubicin or weekly paclitaxel has been evaluated as therapy for recurrence, but response rates have been extremely low (eg, 12% with doxorubicin, 1 26.4% with weekly paclitaxel 2). Long-term survival is diminished for women with stage III or IV cancers, with most series suggesting just a 25% survival rate at 5 years. Despite primary surgery and chemotherapy and even radiation therapy, disease recurrence rates in advanced-stage cases are high. Primary treatment of metastatic recurrent endometrial cancer has been relatively unchanged since the early 2000s. “There is no standard second-line therapy for recurrent endometrial cancer.” Profound change was needed to find agents that would treat these cancers and give patients more time. I remember distinctly listening over and over to a statement made by nearly all the presenters. ![]() The topic of the meeting was on how to design the next endometrial cancer trials. Food and Drug Administration was present. I had the privilege of sitting in a meeting on the treatment of endometrial cancer as a junior investigator in January 2015 where a representative from the U.S. ![]()
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