Dostarlimab Shows Potential as Treatment for Endometrial Cancer: Study

Endometrial cancer, also known as uterine cancer, is a type of malignancy that affects the lining of the uterus, called the endometrium. It is one of the most common gynecologic cancers and primarily affects postmenopausal women. Endometrial cancer develops when abnormal cells in the endometrium grow and multiply uncontrollably, forming a tumor.  

The exact cause of endometrial cancer is not fully understood, but several risk factors have been identified. These include hormonal imbalances, such as an excess of estrogen relative to progesterone, obesity, age (typically affecting women over 50), a history of certain reproductive conditions (e.g., polycystic ovary syndrome and endometrial hyperplasia), a family history of endometrial or colorectal cancer, and certain genetic syndromes (e.g., Lynch syndrome). 

The symptoms of endometrial cancer may vary but often include abnormal vaginal bleeding, particularly postmenopausal bleeding or bleeding between menstrual periods. Other potential signs and symptoms include pelvic pain, a feeling of heaviness in the pelvis, pain during sexual intercourse, and changes in urinary or bowel habits.  

Early detection and diagnosis are crucial for improving the prognosis of endometrial cancer. Diagnostic procedures commonly used include transvaginal ultrasound, endometrial biopsy, hysteroscopy, and dilation and curettage (D&C). Once a diagnosis is confirmed, further staging and evaluation are performed to determine the extent of the disease.  

A recent phase 3 clinical trial published in the New England Journal of Medicine has demonstrated that dostarlimab, an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor, shows promising results in the treatment of endometrial cancer when combined with chemotherapy. The trial was a double-blind, randomized, placebo-controlled study involving patients with primary advanced stage III or IV or first recurrent endometrial cancer. 

118 (or 23.9%) of the 494 individuals had malignancies with high levels of microsatellite instability (MSI-H) and deficient mismatch repair (dMMR). At 24 months, patients with dMMR-MSI-H had a progression-free survival rate of 61.4% in the dostarlimab group and 15.7% in the placebo group. Dostarlimab significantly decreased the chance of progression or death in this group (hazard ratio, 0.28; P 0.001). 

Dostarlimab treatment resulted in a statistically significant increase (hazard ratio, 0.64; P0.001) in progression-free survival at 24 months: 36.1% in the dostarlimab group versus 18.1% in the placebo group. Furthermore, the hazard ratio for death with dostarlimab was 0.64 after 24 months compared to 56.0% with placebo. 

The most often reported unfavorable effects to treatment were nausea, alopecia (hair loss), and tiredness. These side effects were observed in both the dostarlimab and placebo groups, but were more prevalent in the former. Dostarlimab patients had a greater risk of serious adverse events than placebo patients. 

The addition of dostarlimab to conventional carboplatin and paclitaxel therapy for patients with primary advanced or recurrent endometrial cancer increases progression-free survival significantly, with the largest impact reported in the dMMR-MSI-H group. According to this study, dostarlimab shows potential as a treatment for endometrial cancer.