Last week, the US Food and Drug Administration (FDA) made a significant announcement, approving a new therapeutic regimen for patients with endometrial cancer. This malignancy, which develops in the lining of the uterus, known as the endometrium, has been a significant clinical challenge. While 81% of women diagnosed with endometrial cancer survive five or more years, the five-year survival rate for distant cases remains less than 20%. The FDA's approval of this new treatment option is a crucial step towards addressing this need for more effective treatments.
The newly approved treatment regimen involves a chemotherapy and immunotherapy combination approach. The FDA approval pairs dostarlimab-gxly (Jemperli, GlaxoSmithKline), an immune checkpoint inhibitor (ICI) that binds to a protein called programmed death-1 (PD-1) on the surface of immune cells, with chemotherapies carboplatin and paclitaxel. Following the combinatorial treatment, the approval permits dostarlimab-gxly monotherapy to continue.
The recently approved approach applies to women with primary endometrial cancer diagnosed at an advanced stage. In addition, patients who have recurrent endometrial cancer classified as “microsatellite instability-high” (MSI-H) or “mismatch repair deficient” (dMMR). MSI-H and dMMR cancers have specific genetic mutations that can impact cancer development and growth.
The FDA approved this treatment based on data from a clinical trial (NCT03981796) referred to as RUBY. Researchers first published data from the trial in the New England Journal of Medicine. More recently, they provided updates from a phase 3 trial at Society of Gynecologic Oncology’s (SGO) 2024 Annual Meeting on Women’s Cancer in March.
In the trial, participants were either given dostarlimab-gxly with carboplatin and paclitaxel, followed by dostarlimab-gxly (ICI group), or placebo with carboplatin and paclitaxel, followed by placebo (Control group). The results were promising, with those in the ICI group showing a significant improvement in progression-free survival, from 7.7 months in the Control group to 30.3 months. Moreover, patients receiving ICI had a 31% lower risk of death compared to those receiving placebo.
Notably, dMMR, MSI-H tumors account for 25 to 30% of endometrial cancers. The approval of this new treatment option, which has shown promising results in the RUBY trial, can provide renewed hope for a significant proportion of endometrial cancer patients and their families, offering reassurance and optimism in the face of this challenging disease.
Sources: GSK Press Release, FDA Press Release, ASCO Post, NEJM
