Dostarlimab-gxly is an immune checkpoint inhibitor that binds to the protein PD-1 on the surface of immune cells and works by keeping cancer cells from suppressing the immune system, allowing the immune system to attack and kill cancer cells.
The RUBY trial, which included 494 patients with primary advanced or recurrent EC, evaluated efficacy.₃
The recommended dose is 500 mg dostarlimab-gxly every 3 weeks for 6 cycles with carboplatin and paclitaxel, followed by 1,000 mg dostarlimab-gxly every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years. Note: Clinicians should administer dostarlimab-gxly before chemotherapy when administered on the same day.
Dostarlimab-gxly was previously approved with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for primary advanced or recurrent EC that is mismatch repair−deficient (dMMR) or microsatellite instability−high (MSI-H). Several reports have noted dostarlimab-gxly plus chemotherapy as the new standard of care for patients with primary advanced or recurrent EC. Patients treated with dostarlimab-gxly plus chemotherapy have a lower risk of cancer becoming more aggressive and a lower risk of death when compared with patients given chemotherapy alone.₄
Durvalumab is an immune checkpoint inhibitor that targets the PD-L1 protein in cancer cells, helping the immune system to identify and attack cancer cells.
Efficacy was established based on findings in the DUO-E trial, which included patients with primary advanced or recurrent EC.₂
The recommended dose is as follows: for patients with a body weight ≥30 kg, 1,120 mg durvalumab with carboplatin plus paclitaxel every 3 weeks for 6 cycles, followed by 1,500 mg durvalumab every 4 weeks; and for patients with a body weight <30 kg, 15 mg/kg durvalumab with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by durvalumab 20 mg/kg every 4 weeks.
Hertler noted that because of new molecular/genetic discoveries, less aggressive treatments can be given to patients at lower risk, and more aggressive treatments can be reserved for those patients deemed at higher risk due to particular molecular subtypes and genetic mutations.
Hertler added that improvements in chemotherapy and radiation treatments have increased patient QOL. Less invasive procedures, such as laparoscopy and robotic-assisted surgery, have largely replaced extensive open procedures. Radiation treatment has also improved and is now more specifically directed at tumor tissue, thereby sparing more normal tissue.
Early screening is, of course, key to successful treatment, according to Hertler. With early diagnosis, 5-year survival rates can be as high as 95 percent. Identification of Lynch syndrome can be key to an early diagnosis because patients with Lynch syndrome are at increased risk of both endometrial and ovarian cancers. Also, because Lynch syndrome is an inherited disease, its detection can identify family members of patients with EC who may be at high risk.
The annual increase in EC was reported to be 1.37% in Hispanic women, 1.30% in Black women, and -0.17% in White women. Women aged 20-29 years had a 4.48% annual increase, and women aged 30-39 years had a 3% annual increase.
Hispanic women aged 30-39 years had the overall largest rate of increase (4.67%), followed by Black women (3.85%) and White women (2.12%) in the same age group.₈
In another study, Hicks and colleagues identified a notable increase in both incidence (39%) and mortality (26%) rates of EC for Black women when compared with rates in White women. In addition, compared to White American women, African American women had a higher prevalence of poor prognostic variables, more comorbidities, lower income levels, and less insurance coverage. The authors also noted that Black women were more frequently undertreated with surgery, chemotherapy, and radiation.₉
HECTOR analyzed tumor images and clinicopathologic data and used that information to estimate distant recurrence risk, outperforming the current gold standard of pathologic and molecular analysis and predicting distant recurrence and benefit of adjuvant chemotherapy.
HECTOR used hematoxylin and eosin−stained whole-slide images (H&E WSI) and tumor stage as input.
According to the authors, HECTOR may have the potential to be a highly effective tool for prognosis in individual patients with EC and may also enable biomarker discoveries for improving targeted treatment decision-making.
CTLA-4 inhibitors boost tumor-specific T-cell activation and proliferation by promoting CD28-mediated costimulation.
PD-1/PD-L1 inhibitors restore the function of tumor-infiltrating T cells by reversing negative signaling.
FDA-approved antibodies targeting these checkpoints include ipilimumab, pembrolizumab, nivolumab, cemiplimab, avelumab, atezolizumab, and durvalumab.
Robotic-assisted surgery showed improved perioperative outcomes, including reduced blood loss, length of hospital stay, intraoperative complications, and incidence of blood transfusion, fever, and ileus. Laparoscopy appears to be the best technique for reducing the incidence of infection, venous thromboembolism, and recurrence.
The authors noted, however, that operating time was increased for minimally invasive techniques compared with open techniques. The increased duration of operating time was 18.95 minutes with laparoscopy and 29 minutes with robotic-assisted surgery.
Mean reductions in length of hospital stay with laparoscopy and robotic-assisted surgery were −3.54 days and −3.79 days, respectively.
According to the Cancer Genome Atlas classification, the subgroups consist of POLE-mutated (POLEmut) EC, EC with microsatellite instability and a deficient mismatch repair pathway (dMMR/MSI), EC with low copy-number alterations (CNAs) and tumor mutational burden (TMB) and a stable microsatellite status (CN-low), and a CN-high subgroup with a high number of CNAs and a low mutation rate.₂₀
Researchers identified potentially actionable alterations in 64% of patients, suggesting a potential benefit from matched therapy.
cfDNA provides a tool to characterize metastatic disease without the need for a new tumor biopsy
Human epidermal growth factor receptor 2 (HER2): Agents under study include AZD8205 (puxitatug samrotecan), SGN-B7H4V (monomethyl auristatin E), trastuzumab deruxtecan (T-DXd), and DB-1303.
Folate receptor-alpha (FRα): Agents being studied include mirvetuximab soravtansine and farletuzumab ecteribulin.₂₂
Trophoblast cell-surface antigen-2 (TROP2): Studies are ongoing for sacituzumab govitecan.
B7-H4: XMT-1660 is currently under study.₂₃
3. Auranen A, Powell MA, Sukhin V, et al. Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY). Ther Adv Med Oncol. 2024;16:17588359241277656. Published 2024 Sep 28. doi:10.1177/17588359241277656
4. Furlow B. Dostarlimab improves OS in advanced, recurrent endometrial cancer. Cancer Therapy Advisor. March 16, 2024. Accessed October 22, 2024.
5. FDA approves durvalumab with chemotherapy for mismatch repair deficient primary advanced or recurrent endometrial cancer. FDA.gov. June 14, 2024. Accessed October 22, 2024.
6. Dr. Andrew Hertler Talks About Current Treatments, Quality of Life for Women With Endometrial Cancer | Docwire News. Formedics. October 11, 2024. Accessed October 23, 2024.
7. Nalley C. Researchers Examine Current Trends in Endometrial Cancer & Obesity. Oncology Times. June 3, 2024. Accessed October 17, 2024.
8. Thomas T. Black Women Disproportionately Affected by Aggressive Endometrial Cancers. Urban Health Today. April 3, 2024. Accessed October 23, 2024.
9. Hicks ML, Hicks MM, Mathews RP, et al. Racial disparities in endometrial cancer: Where are we after 26 years? Gynecol Oncol. 2024;184:236-242. doi:10.1016/j.ygyno.2024.01.054
10. The Latest in Endometrial Cancer: Liquid Profiling, LVSI, and More - Physician's Weekly (physiciansweekly.com). Formedics. Oct 2, 2024. Accessed October 23, 2024.
11. Volinsky-Fremond S, Horeweg N, Andani S, et al. Prediction of recurrence risk in endometrial cancer with multimodal deep learning [published correction appears in Nat Med. 2024 Jul;30(7):2092. doi: 10.1038/s41591-024-03126-z]. Nat Med. 2024;30(7):1962-1973. doi:10.1038/s41591-024-02993-w
12. Predicting Endometrial Cancer Recurrence With a Deep Learning Model. Physician's Weekly (physiciansweekly.com). Formedics. Aug 22, 2024. Accessed
